Immune Checkpoint Inhibitors in Renal Cell Carcinoma: Molecular Basis and Rationale for Their Use in Clinical Practice
Abstract
:1. Introduction
2. Cancer Immune Surveillance and Escape Mechanisms
3. Immunometabolic Rewiring of Cancer
4. Immunotherapy in RCC
5. Mechanism of Action of ICIs
5.1. Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4)
5.2. Programmed Cell Death Protein-1 and Its Ligand (PD-1/PD-L1)
5.3. T Cell Immunoglobulin and Mucin Domain-Containing 3 (TIM-3)
5.4. T Cell Immunoreceptor with Immunoglobulin and ITIM Domain (TIGIT)
5.5. Lymphocyte Activation Gene-3 (LAG-3)
5.6. Indoleamine 2,3-Dioxyegenase 1 (IDO1)
5.7. V-Domain Immunoglobulin Suppressor of T Cell Activation (VISTA)
6. Use of Immune Checkpoint Inhibitors (ICIs) in Clinical Settings
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Siegel, R.L.; Miller, K.D.; Wagle, N.S.; Jemal, A. Cancer statistics, 2023. CA A Cancer J. Clin. 2023, 73, 17–48. [Google Scholar] [CrossRef]
- di Meo, N.A.; Lasorsa, F.; Rutigliano, M.; Loizzo, D.; Ferro, M.; Stella, A.; Bizzoca, C.; Vincenti, L.; Pandolfo, S.D.; Autorino, R.; et al. Renal Cell Carcinoma as a Metabolic Disease: An Update on Main Pathways, Potential Biomarkers, and Therapeutic Targets. Int. J. Mol. Sci. 2022, 23, 14360. [Google Scholar] [CrossRef]
- Lucarelli, G.; Rutigliano, M.; Sallustio, F.; Ribatti, D.; Giglio, A.; Signorile, M.L.; Grossi, V.; Sanese, P.; Napoli, A.; Maiorano, E.; et al. Integrated multi-omics characterization reveals a distinctive metabolic signature and the role of NDUFA4L2 in promoting angiogenesis, chemoresistance, and mitochondrial dysfunction in clear cell renal cell carcinoma. Aging 2018, 10, 3957–3985. [Google Scholar] [CrossRef]
- Lucarelli, G.; Loizzo, D.; Franzin, R.; Battaglia, S.; Ferro, M.; Cantiello, F.; Castellano, G.; Bettocchi, C.; Ditonno, P.; Battaglia, M. Metabolomic insights into pathophysiological mechanisms and biomarker discovery in clear cell renal cell carcinoma. Expert Rev. Mol. Diagn. 2019, 19, 397–407. [Google Scholar] [CrossRef]
- Lucarelli, G.; Ferro, M.; Loizzo, D.; Bianchi, C.; Terracciano, D.; Cantiello, F.; Bell, L.N.; Battaglia, S.; Porta, C.; Gernone, A.; et al. Integration of Lipidomics and Transcriptomics Reveals Reprogramming of the Lipid Metabolism and Composition in Clear Cell Renal Cell Carcinoma. Metabolites 2020, 10, 509. [Google Scholar] [CrossRef]
- De Marco, S.; Torsello, B.; Minutiello, E.; Morabito, I.; Grasselli, C.; Bombelli, S.; Zucchini, N.; Lucarelli, G.; Strada, G.; Perego, R.A.; et al. The cross-talk between Abl2 tyrosine kinase and TGFβ1 signalling modulates the invasion of clear cell Renal Cell Carcinoma cells. FEBS Lett. 2022. [Google Scholar] [CrossRef]
- Bianchi, C.; Meregalli, C.; Bombelli, S.; Di Stefano, V.; Salerno, F.; Torsello, B.; De Marco, S.; Bovo, G.; Cifola, I.; Mangano, E.; et al. The glucose and lipid metabolism reprogramming is grade-dependent in clear cell renal cell carcinoma primary cultures and is targetable to modulate cell viability and proliferation. Oncotarget 2017, 8, 113502–113515. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lucarelli, G.; Rutigliano, M.; Sanguedolce, F.; Galleggiante, V.; Giglio, A.; Cagiano, S.; Bufo, P.; Maiorano, E.; Ribatti, D.; Ranieri, E.; et al. Increased Expression of the Autocrine Motility Factor is Associated With Poor Prognosis in Patients With Clear Cell–Renal Cell Carcinoma. Medicine 2015, 94, e2117. [Google Scholar] [CrossRef]
- Lucarelli, G.; Galleggiante, V.; Rutigliano, M.; Sanguedolce, F.; Cagiano, S.; Bufo, P.; Lastilla, G.; Maiorano, E.; Ribatti, D.; Giglio, A.; et al. Metabolomic profile of glycolysis and the pentose phosphate pathway identifies the central role of glucose-6-phosphate dehydrogenase in clear cell-renal cell carcinoma. Oncotarget 2015, 6, 13371–13386. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lucarelli, G.; Ferro, M.; Ditonno, P.; Battaglia, M. The urea cycle enzymes act as metabolic suppressors in clear cell renal cell carcinoma. Transl. Cancer Res. 2018, 7, S766–S769. [Google Scholar] [CrossRef] [Green Version]
- Bombelli, S.; Torsello, B.; De Marco, S.; Lucarelli, G.; Cifola, I.; Grasselli, C.; Strada, G.; Bovo, G.; Perego, R.A.; Bianchi, C. 36-kDa Annexin A3 Isoform Negatively Modulates Lipid Storage in Clear Cell Renal Cell Carcinoma Cells. Am. J. Pathol. 2020, 190, 2317–2326. [Google Scholar] [CrossRef]
- Lucarelli, G.; Ferro, M.; Battaglia, M. Multi-omics approach reveals the secrets of metabolism of clear cell—Renal cell carcinoma. Transl. Androl. Urol. 2016, 5, 801–803. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ragone, R.; Sallustio, F.; Piccinonna, S.; Rutigliano, M.; Vanessa, G.; Palazzo, S.; Lucarelli, G.; Ditonno, P.; Battaglia, M.; Fanizzi, F.P.; et al. Renal Cell Carcinoma: A Study through NMR-Based Metabolomics Combined with Transcriptomics. Diseases 2016, 4, 7. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- di Meo, N.A.; Lasorsa, F.; Rutigliano, M.; Milella, M.; Ferro, M.; Battaglia, M.; Ditonno, P.; Lucarelli, G. The dark side of lipid metabolism in prostate and renal carcinoma: Novel insights into molecular diagnostic and biomarker discovery. Expert Rev. Mol. Diagn. 2023, 1–17. [Google Scholar] [CrossRef]
- Ferro, M.; Musi, G.; Marchioni, M.; Maggi, M.; Veccia, A.; Del Giudice, F.; Barone, B.; Crocetto, F.; Lasorsa, F.; Antonelli, A.; et al. Radiogenomics in Renal Cancer Management—Current Evidence and Future Prospects. Int. J. Mol. Sci. 2023, 24, 4615. [Google Scholar] [CrossRef]
- Tataru, O.S.; Marchioni, M.; Crocetto, F.; Barone, B.; Lucarelli, G.; Del Giudice, F.; Busetto, G.M.; Veccia, A.; Giudice, A.L.; Russo, G.I.; et al. Molecular Imaging Diagnosis of Renal Cancer Using 99mTc-Sestamibi SPECT/CT and Girentuximab PET-CT-Current Evidence and Future Development of Novel Techniques. Diagnostics 2023, 13, 593. [Google Scholar] [CrossRef]
- Papale, M.; Vocino, G.; Lucarelli, G.; Rutigliano, M.; Gigante, M.; Rocchetti, M.T.; Pesce, F.; Sanguedolce, F.; Bufo, P.; Battaglia, M.; et al. Urinary RKIP/p-RKIP is a potential diagnostic and prognostic marker of clear cell renal cell carcinoma. Oncotarget 2017, 8, 40412–40424. [Google Scholar] [CrossRef] [Green Version]
- Gigante, M.; Lucarelli, G.; Divella, C.; Netti, G.S.; Pontrelli, P.; Cafiero, C.; Grandaliano, G.; Castellano, G.; Rutigliano, M.; Stallone, G.; et al. Soluble Serum αKlotho Is a Potential Predictive Marker of Disease Progression in Clear Cell Renal Cell Carcinoma. Medicine 2015, 94, e1917. [Google Scholar] [CrossRef] [PubMed]
- Galleggiante, V.; Rutigliano, M.; Sallustio, F.; Ribatti, D.; Ditonno, P.; Bettocchi, C.; Selvaggi, F.P.; Lucarelli, G.; Battaglia, M. CTR2 Identifies a Population of Cancer Cells with Stem Cell-like Features in Patients with Clear Cell Renal Cell Carcinoma. J. Urol. 2014, 192, 1831–1841. [Google Scholar] [CrossRef] [PubMed]
- Monti, M.; Lunardini, S.; Magli, I.A.; Campi, R.; Primiceri, G.; Berardinelli, F.; Amparore, D.; Terracciano, D.; Lucarelli, G.; Schips, L.; et al. Micro-RNAs Predict Response to Systemic Treatments in Metastatic Renal Cell Carcinoma Patients: Results from a Systematic Review of the Literature. Biomedicines 2022, 10, 1287. [Google Scholar] [CrossRef] [PubMed]
- Battaglia, M.; Lucarelli, G. The Role of Renal Surgery in the Era of Targeted Therapy: The Urologist’s Perspective. Urol. J. 2015, 82, 137–138. [Google Scholar] [CrossRef]
- The Basics of Cancer Immunotherapy; Springer Science+Business Media: New York, NY, USA, 2018; ISBN 978-3-319-70621-4.
- Abbas, A.K.; Lichtman, A.H.; Pillai, S. Cellular and Molecular Immunology, 8th ed.; Elsevier Saunders: Philadelphia, PA, USA, 2015; ISBN 978-0-323-22275-4. [Google Scholar]
- Lundon, D.J.; Kelly, B.D.; Nusrat, N.B.; Foley, R.W.; D’Arcy, F.T.; Jaffry, S.Q. Renal Cell Carcinoma Presenting as Painless Jaundice and Unintentional Weight Loss. Am. J. Clin. Exp. Urol. 2022, 10, 408–411. [Google Scholar] [PubMed]
- Chen, X.; Hao, S.; Zhao, Z.; Liu, J.; Shao, Q.; Wang, F.; Sun, D.; He, Y.; Gao, W.; Mao, H. Interleukin 35: Inhibitory regulator in monocyte-derived dendritic cell maturation and activation. Cytokine 2018, 108, 43–52. [Google Scholar] [CrossRef] [PubMed]
- Kitamura, H.; Ohno, Y.; Toyoshima, Y.; Ohtake, J.; Homma, S.; Kawamura, H.; Takahashi, N.; Taketomi, A. Interleukin-6/STAT3 signaling as a promising target to improve the efficacy of cancer immunotherapy. Cancer Sci. 2017, 108, 1947–1952. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Veglia, F.; Tyurin, V.A.; Mohammadyani, D.; Blasi, M.; Duperret, E.K.; Donthireddy, L.; Hashimoto, A.; Kapralov, A.; Amoscato, A.; Angelini, R.; et al. Lipid bodies containing oxidatively truncated lipids block antigen cross-presentation by dendritic cells in cancer. Nat. Commun. 2017, 8, 2122. [Google Scholar] [CrossRef] [Green Version]
- Tseng, D.; Volkmer, J.-P.; Willingham, S.B.; Contreras-Trujillo, H.; Fathman, J.W.; Fernhoff, N.B.; Seita, J.; Inlay, M.A.; Weiskopf, K.; Miyanishi, M.; et al. Anti-CD47 antibody–mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response. Proc. Natl. Acad. Sci. USA 2013, 110, 11103–11108. [Google Scholar] [CrossRef] [Green Version]
- Park, H.; Jee, S.; Bang, S.; Son, H.; Cha, H.; Myung, J.; Sim, J.; Kim, Y.; Paik, S.; Kim, H. CD47 Expression Predicts Unfavorable Prognosis in Clear Cell Renal Cell Carcinoma after Curative Resection. Diagnostics 2022, 12, 2291. [Google Scholar] [CrossRef]
- Ling, A.; Löfgren-Burström, A.; Larsson, P.; Li, X.; Wikberg, M.L.; Öberg, Å.; Stenling, R.; Edin, S.; Palmqvist, R. TAP1 down-regulation elicits immune escape and poor prognosis in colorectal cancer. Oncoimmunology 2017, 6, e1356143. [Google Scholar] [CrossRef] [Green Version]
- Shionoya, Y.; Kanaseki, T.; Miyamoto, S.; Tokita, S.; Hongo, A.; Kikuchi, Y.; Kochin, V.; Watanabe, K.; Horibe, R.; Saijo, H.; et al. Loss of tapasin in human lung and colon cancer cells and escape from tumor-associated antigen-specific CTL recognition. Oncoimmunology 2017, 6, e1274476. [Google Scholar] [CrossRef] [Green Version]
- Yarchoan, M.; Johnson, B.A.; Lutz, E.R.; Laheru, D.A.; Jaffee, E.M. Erratum: Targeting neoantigens to augment antitumour immunity. Nat. Rev. Cancer 2017, 17, 569. [Google Scholar] [CrossRef] [Green Version]
- Dirkx, A.E.M.; Egbrink, M.G.A.O.; E Kuijpers, M.J.; Van Der Niet, S.T.; Heijnen, V.V.T.; Steege, J.C.A.B.-T.; Wagstaff, J.; Griffioen, A.W. Tumor angiogenesis modulates leukocyte-vessel wall interactions in vivo by reducing endothelial adhesion molecule expression. Cancer Res. 2003, 63, 2322–2329. [Google Scholar]
- Apte, R.S.; Chen, D.S.; Ferrara, N. VEGF in Signaling and Disease: Beyond Discovery and Development. Cell 2019, 176, 1248–1264. [Google Scholar] [CrossRef] [Green Version]
- Buckanovich, R.J.; Facciabene, A.; Kim, S.; Benencia, F.; Sasaroli, D.; Balint, K.; Katsaros, D.; O’Brien-Jenkins, A.; A Gimotty, P.; Coukos, G. Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy. Nat. Med. 2008, 14, 28–36. [Google Scholar] [CrossRef]
- Pardoll, D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 2012, 12, 252–264. [Google Scholar] [CrossRef] [Green Version]
- Tseng, S.-Y.; Otsuji, M.; Gorski, K.; Huang, X.; Slansky, J.E.; Pai, S.I.; Shalabi, A.; Shin, T.; Pardoll, D.M.; Tsuchiya, H. B7-Dc, a New Dendritic Cell Molecule with Potent Costimulatory Properties for T Cells. J. Exp. Med. 2001, 193, 839–846. [Google Scholar] [CrossRef] [PubMed]
- Latchman, Y.; Wood, C.R.; Chernova, T.; Chaudhary, D.; Borde, M.; Chernova, I.; Iwai, Y.; Long, A.J.; Brown, J.A.; Nunes, R.; et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat. Immunol. 2001, 2, 261–268. [Google Scholar] [CrossRef] [PubMed]
- Yao, S.; Zhu, Y.; Chen, L. Advances in targeting cell surface signalling molecules for immune modulation. Nat. Rev. Drug Discov. 2013, 12, 130–146. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Takamatsu, K.; Tanaka, N.; Hakozaki, K.; Takahashi, R.; Teranishi, Y.; Murakami, T.; Kufukihara, R.; Niwa, N.; Mikami, S.; Shinojima, T.; et al. Profiling the inhibitory receptors LAG-3, TIM-3, and TIGIT in renal cell carcinoma reveals malignancy. Nat. Commun. 2021, 12, 5547. [Google Scholar] [CrossRef]
- Lin, C.; He, H.; Liu, H.; Li, R.; Chen, Y.; Qi, Y.; Jiang, Q.; Chen, L.; Zhang, P.; Zhang, H.; et al. Tumour-associated macrophages-derived CXCL8 determines immune evasion through autonomous PD-L1 expression in gastric cancer. Gut 2019, 68, 1764–1773. [Google Scholar] [CrossRef]
- Tamma, R.; Rutigliano, M.; Lucarelli, G.; Annese, T.; Ruggieri, S.; Cascardi, E.; Napoli, A.; Battaglia, M.; Ribatti, D. Microvascular density, macrophages, and mast cells in human clear cell renal carcinoma with and without bevacizumab treatment. Urol. Oncol. Semin. Orig. Investig. 2019, 37, 355.e11–355.e19. [Google Scholar] [CrossRef] [PubMed]
- Lucarelli, G.; Rutigliano, M.; Loizzo, D.; di Meo, N.A.; Lasorsa, F.; Mastropasqua, M.; Maiorano, E.; Bizzoca, C.; Vincenti, L.; Battaglia, M.; et al. MUC1 Tissue Expression and Its Soluble Form CA15-3 Identify a Clear Cell Renal Cell Carcinoma with Distinct Metabolic Profile and Poor Clinical Outcome. Int. J. Mol. Sci. 2022, 23, 13968. [Google Scholar] [CrossRef] [PubMed]
- Lucarelli, G.; Netti, G.S.; Rutigliano, M.; Lasorsa, F.; Loizzo, D.; Milella, M.; Schirinzi, A.; Fontana, A.; Di Serio, F.; Tamma, R.; et al. MUC1 Expression Affects the Immunoflogosis in Renal Cell Carcinoma Microenvironment through Complement System Activation and Immune Infiltrate Modulation. Int. J. Mol. Sci. 2023, 24, 4814. [Google Scholar] [CrossRef] [PubMed]
- Netti, G.S.; Lucarelli, G.; Spadaccino, F.; Castellano, G.; Gigante, M.; Divella, C.; Rocchetti, M.T.; Rascio, F.; Mancini, V.; Stallone, G.; et al. PTX3 modulates the immunoflogosis in tumor microenvironment and is a prognostic factor for patients with clear cell renal cell carcinoma. Aging 2020, 12, 7585–7602. [Google Scholar] [CrossRef] [PubMed]
- Lucarelli, G.; Ditonno, P.; Bettocchi, C.; Vavallo, A.; Rutigliano, M.; Galleggiante, V.; LaRocca, A.M.V.; Castellano, G.; Gesualdo, L.; Grandaliano, G.; et al. Diagnostic and Prognostic Role of Preoperative Circulating CA 15-3, CA 125, and Beta-2 Microglobulin in Renal Cell Carcinoma. Dis. Markers 2014, 2014, 689795. [Google Scholar] [CrossRef]
- Phillips, M.M.; Sheaff, M.T.; Szlosarek, P.W. Targeting Arginine-Dependent Cancers with Arginine-Degrading Enzymes: Opportunities and Challenges. Cancer Res. Treat. 2013, 45, 251–262. [Google Scholar] [CrossRef] [PubMed]
- Lucarelli, G.; Rutigliano, M.; Ferro, M.; Giglio, A.; Intini, A.; Triggiano, F.; Palazzo, S.; Gigante, M.; Castellano, G.; Ranieri, E.; et al. Activation of the kynurenine pathway predicts poor outcome in patients with clear cell renal cell carcinoma. Urol. Oncol. Semin. Orig. Investig. 2017, 35, 461.e15–461.e27. [Google Scholar] [CrossRef]
- Lasorsa, F.; di Meo, N.A.; Rutigliano, M.; Ferro, M.; Terracciano, D.; Tataru, O.S.; Battaglia, M.; Ditonno, P.; Lucarelli, G. Emerging Hallmarks of Metabolic Reprogramming in Prostate Cancer. Int. J. Mol. Sci. 2023, 24, 910. [Google Scholar] [CrossRef]
- Di Gennaro, P.; Gerlini, G.; Caporale, R.; Sestini, S.; Brandani, P.; Urso, C.; Pimpinelli, N.; Borgognoni, L. T regulatory cells mediate immunosuppresion by adenosine in peripheral blood, sentinel lymph node and TILs from melanoma patients. Cancer Lett. 2018, 417, 124–130. [Google Scholar] [CrossRef]
- Togashi, Y.; Shitara, K.; Nishikawa, H. Regulatory T cells in cancer immunosuppression—Implications for anticancer therapy. Nat. Rev. Clin. Oncol. 2019, 16, 356–371. [Google Scholar] [CrossRef]
- Gigante, M.; Pontrelli, P.; Herr, W.; Gigante, M.; D’Avenia, M.; Zaza, G.; Cavalcanti, E.; Accetturo, M.; Lucarelli, G.; Carrieri, G.; et al. miR-29b and miR-198 overexpression in CD8+ T cells of renal cell carcinoma patients down-modulates JAK3 and MCL-1 leading to immune dysfunction. J. Transl. Med. 2016, 14, 84. [Google Scholar] [CrossRef] [Green Version]
- Taylor, N.A.; Vick, S.C.; Iglesia, M.D.; Brickey, W.J.; Midkiff, B.R.; McKinnon, K.P.; Reisdorf, S.; Anders, C.K.; Carey, L.A.; Parker, J.S.; et al. Treg depletion potentiates checkpoint inhibition in claudin-low breast cancer. J. Clin. Investig. 2017, 127, 3472–3483. [Google Scholar] [CrossRef] [Green Version]
- Xia, L.; Oyang, L.; Lin, J.; Tan, S.; Han, Y.; Wu, N.; Yi, P.; Tang, L.; Pan, Q.; Rao, S.; et al. The cancer metabolic reprogramming and immune response. Mol. Cancer 2021, 20, 28. [Google Scholar] [CrossRef]
- Lian, X.; Yang, K.; Li, R.; Li, M.; Zuo, J.; Zheng, B.; Wang, W.; Wang, P.; Zhou, S. Immunometabolic rewiring in tumorigenesis and anti-tumor immunotherapy. Mol. Cancer 2022, 21, 27. [Google Scholar] [CrossRef] [PubMed]
- Ricciardi, S.; Manfrini, N.; Alfieri, R.; Calamita, P.; Crosti, M.C.; Gallo, S.; Müller, R.; Pagani, M.; Abrignani, S.; Biffo, S. The Translational Machinery of Human CD4+ T Cells Is Poised for Activation and Controls the Switch from Quiescence to Metabolic Remodeling. Cell Metab. 2018, 28, 895–906.e5. [Google Scholar] [CrossRef] [Green Version]
- Pearce, E.L.; Pearce, E.J. Metabolic Pathways in Immune Cell Activation and Quiescence. Immunity 2013, 38, 633–643. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Singer, K.; Kastenberger, M.; Gottfried, E.; Hammerschmied, C.G.; Büttner, M.; Aigner, M.; Seliger, B.; Walter, B.; Schlösser, H.; Hartmann, A.; et al. Warburg phenotype in renal cell carcinoma: High expression of glucose-transporter 1 (GLUT-1) correlates with low CD8+ T-cell infiltration in the tumor. Int. J. Cancer 2011, 128, 2085–2095. [Google Scholar] [CrossRef]
- Brand, A.; Singer, K.; Koehl, G.E.; Kolitzus, M.; Schoenhammer, G.; Thiel, A.; Matos, C.; Bruss, C.; Klobuch, S.; Peter, K.; et al. LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells. Cell Metab. 2016, 24, 657–671. [Google Scholar] [CrossRef] [Green Version]
- Perrone, F.; Minari, R.; Bersanelli, M.; Bordi, P.; Tiseo, M.; Favari, E.; Sabato, R.; Buti, S. The Prognostic Role of High Blood Cholesterol in Advanced Cancer Patients Treated With Immune Checkpoint Inhibitors. J. Immunother. 2020, 43, 196–203. [Google Scholar] [CrossRef] [PubMed]
- Barré, C.; Vérine, J.L.; Régnier, J.; Enon, B.; Houssin, A.; Chaigné, P.; Soret, J.Y. Spontaneous regression of regressive pulmonary metastases from kidney cancer. Myth or reality? Apropos of 2 cases. Ann. Durologie 1986, 20, 275–279. [Google Scholar]
- Fyfe, G.; Fisher, R.I.; Rosenberg, S.A.; Sznol, M.; Parkinson, D.R.; Louie, A.C. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J. Clin. Oncol. 1995, 13, 688–696. [Google Scholar] [CrossRef]
- Dekernion, J.; Sarna, G.; Figlin, R.; Lindner, A.; Smith, R.B. The Treatment of Renal Cell Carcinoma with Human Leukocyte Alpha-Interferon. J. Urol. 1983, 130, 1063–1066. [Google Scholar] [CrossRef] [PubMed]
- Charych, D.H.; Hoch, U.; Langowski, J.L.; Lee, S.R.; Addepalli, M.K.; Kirk, P.B.; Sheng, D.; Liu, X.; Sims, P.W.; VanderVeen, L.A.; et al. NKTR-214, an Engineered Cytokine with Biased IL2 Receptor Binding, Increased Tumor Exposure, and Marked Efficacy in Mouse Tumor Models. Clin. Cancer Res. 2016, 22, 680–690. [Google Scholar] [CrossRef] [Green Version]
- Escudier, B.; Pluzanska, A.; Koralewski, P.; Ravaud, A.; Bracarda, S.; Szczylik, C.; Chevreau, C.; Filipek, M.; Melichar, B.; Bajetta, E.; et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: A randomised, double-blind phase III trial. Lancet 2008, 370, 2103–2111. [Google Scholar] [CrossRef] [PubMed]
- Rini, B.I.; Halabi, S.; Rosenberg, J.E.; Stadler, W.M.; Vaena, D.A.; Ou, S.-S.; Archer, L.; Atkins, J.N.; Picus, J.; Czaykowski, P.; et al. Bevacizumab Plus Interferon Alfa Compared With Interferon Alfa Monotherapy in Patients With Metastatic Renal Cell Carcinoma: CALGB 90206. J. Clin. Oncol. 2008, 26, 5422–5428. [Google Scholar] [CrossRef]
- Liu, Y.-F.; Zhang, Z.-C.; Wang, S.-Y.; Fu, S.-Q.; Cheng, X.-F.; Chen, R.; Sun, T. Immune checkpoint inhibitor-based therapy for advanced clear cell renal cell carcinoma: A narrative review. Int. Immunopharmacol. 2022, 110, 108900. [Google Scholar] [CrossRef] [PubMed]
- Linsley, P.S.; Bradshaw, J.; Greene, J.; Peach, R.; Bennett, K.L.; Mittler, R.S. Intracellular Trafficking of CTLA-4 and Focal Localization Towards Sites of TCR Engagement. Immunity 1996, 4, 535–543. [Google Scholar] [CrossRef] [Green Version]
- Schildberg, F.A.; Klein, S.R.; Freeman, G.J.; Sharpe, A.H. Coinhibitory Pathways in the B7-CD28 Ligand-Receptor Family. Immunity 2016, 44, 955–972. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, C.; Chen, J.; Song, Q.; Sun, X.; Xue, M.; Yang, Z.; Shang, J. Comprehensive analysis of CTLA-4 in the tumor immune microenvironment of 33 cancer types. Int. Immunopharmacol. 2020, 85, 106633. [Google Scholar] [CrossRef]
- Zhang, X.; Yin, X.; Zhang, H.; Sun, G.; Yang, Y.; Chen, J.; Zhu, X.; Zhao, P.; Zhao, J.; Liu, J.; et al. Differential expressions of PD-1, PD-L1 and PD-L2 between primary and metastatic sites in renal cell carcinoma. BMC Cancer 2019, 19, 360. [Google Scholar] [CrossRef] [Green Version]
- Patsoukis, N.; Brown, J.; Petkova, V.; Liu, F.; Li, L.; Boussiotis, V.A. Selective Effects of PD-1 on Akt and Ras Pathways Regulate Molecular Components of the Cell Cycle and Inhibit T Cell Proliferation. Sci. Signal. 2012, 5, ra46. [Google Scholar] [CrossRef] [Green Version]
- Francisco, L.M.; Salinas, V.H.; Brown, K.E.; Vanguri, V.K.; Freeman, G.J.; Kuchroo, V.K.; Sharpe, A.H. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J. Exp. Med. 2009, 206, 3015–3029. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Andrews, L.P.; Yano, H.; Vignali, D.A.A. Inhibitory receptors and ligands beyond PD-1, PD-L1 and CTLA-4: Breakthroughs or backups. Nat. Immunol. 2019, 20, 1425–1434. [Google Scholar] [CrossRef] [PubMed]
- Jang, A.; Sweeney, P.L.; Barata, P.C.; Koshkin, V.S. PD-L1 Expression and Treatment Implications in Metastatic Clear Cell Renal Cell Carcinoma: A Systematic Review. Kidney Cancer 2021, 5, 31–46. [Google Scholar] [CrossRef]
- Kammerer-Jacquet, S.-F.; Brunot, A.; Lefort, M.; Bayat, S.; Peyronnet, B.; Verhoest, G.; Mathieu, R.; Lespagnol, A.; Mosser, J.; Laguerre, B.; et al. Metastatic Clear-cell Renal Cell Carcinoma With a Long-term Response to Sunitinib: A Distinct Phenotype Independently Associated With Low PD-L1 Expression. Clin. Genitourin. Cancer 2019, 17, 169–176.e1. [Google Scholar] [CrossRef]
- Das, M.; Zhu, C.; Kuchroo, V.K. Tim-3 and its role in regulating anti-tumor immunity. Immunol. Rev. 2017, 276, 97–111. [Google Scholar] [CrossRef] [Green Version]
- Meyers, J.H.; Sabatos, C.A.; Chakravarti, S.; Kuchroo, V.K. The TIM gene family regulates autoimmune and allergic diseases. Trends Mol. Med. 2005, 11, 362–369. [Google Scholar] [CrossRef] [PubMed]
- Zhu, C.; Anderson, A.C.; Schubart, A.; Xiong, H.; Imitola, J.; Khoury, S.; Zheng, X.X.; Strom, T.B.; Kuchroo, V.K. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat. Immunol. 2005, 6, 1245–1252. [Google Scholar] [CrossRef] [PubMed]
- Chiba, S.; Baghdadi, M.; Akiba, H.; Yoshiyama, H.; Kinoshita, I.; Dosaka-Akita, H.; Fujioka, Y.; Ohba, Y.; Gorman, J.V.; Colgan, J.D.; et al. Tumor-infiltrating DCs suppress nucleic acid–mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat. Immunol. 2012, 13, 832–842. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Voron, T.; Colussi, O.; Marcheteau, E.; Pernot, S.; Nizard, M.; Pointet, A.-L.; Latreche, S.; Bergaya, S.; Benhamouda, N.; Tanchot, C.; et al. VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors. J. Exp. Med. 2015, 212, 139–148. [Google Scholar] [CrossRef]
- Granier, C.; Dariane, C.; Combe, P.; Verkarre, V.; Urien, S.; Badoual, C.; Roussel, H.; Mandavit, M.; Ravel, P.; Sibony, M.; et al. Tim-3 Expression on Tumor-Infiltrating PD-1+CD8+ T Cells Correlates with Poor Clinical Outcome in Renal Cell Carcinoma. Cancer Res. 2017, 77, 1075–1082. [Google Scholar] [CrossRef] [Green Version]
- Gorman, J.V.; Starbeck-Miller, G.; Pham, N.-L.L.; Traver, G.L.; Rothman, P.B.; Harty, J.T.; Colgan, J.D. Tim-3 Directly Enhances CD8 T Cell Responses to Acute Listeria monocytogenes Infection. J. Immunol. 2014, 192, 3133–3142. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gleason, M.K.; Lenvik, T.R.; McCullar, V.; Felices, M.; O’Brien, M.S.; Cooley, S.A.; Verneris, M.R.; Cichocki, F.; Holman, C.J.; Panoskaltsis-Mortari, A.; et al. Tim-3 is an inducible human natural killer cell receptor that enhances interferon gamma production in response to galectin-9. Blood 2012, 119, 3064–3072. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yu, X.; Harden, K.; Gonzalez, L.C.; Francesco, M.; Chiang, E.; A Irving, B.; Tom, I.; Ivelja, S.; Refino, C.J.; Clark, H.; et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat. Immunol. 2008, 10, 48–57. [Google Scholar] [CrossRef] [PubMed]
- Chauvin, J.-M.; Zarour, H.M. TIGIT in cancer immunotherapy. J. Immunother. Cancer 2020, 8, e000957. [Google Scholar] [CrossRef]
- Joller, N.; Lozano, E.; Burkett, P.R.; Patel, B.; Xiao, S.; Zhu, C.; Xia, J.; Tan, T.G.; Sefik, E.; Yajnik, V.; et al. Treg Cells Expressing the Coinhibitory Molecule TIGIT Selectively Inhibit Proinflammatory Th1 and Th17 Cell Responses. Immunity 2014, 40, 569–581. [Google Scholar] [CrossRef] [Green Version]
- Kurtulus, S.; Sakuishi, K.; Ngiow, S.-F.; Joller, N.; Tan, D.J.; Teng, M.; Smyth, M.; Kuchroo, V.K.; Anderson, A.C. TIGIT predominantly regulates the immune response via regulatory T cells. J. Clin. Investig. 2015, 125, 4053–4062. [Google Scholar] [CrossRef] [Green Version]
- Joller, N.; Hafler, J.P.; Brynedal, B.; Kassam, N.; Spoerl, S.; Levin, S.D.; Sharpe, A.H.; Kuchroo, V.K. Cutting Edge: TIGIT Has T Cell-Intrinsic Inhibitory Functions. J. Immunol. 2011, 186, 1338–1342. [Google Scholar] [CrossRef] [Green Version]
- Chauvin, J.-M.; Pagliano, O.; Fourcade, J.; Sun, Z.; Wang, H.; Sander, C.; Kirkwood, J.M.; Chen, T.-H.T.; Maurer, M.; Korman, A.J.; et al. TIGIT and PD-1 impair tumor antigen–specific CD8+ T cells in melanoma patients. J. Clin. Investig. 2015, 125, 2046–2058. [Google Scholar] [CrossRef]
- Hong, X.; Wang, X.; Wang, T.; Zhang, X. Correlation of T Cell Immunoglobulin and ITIM Domain (TIGIT) and Programmed Death 1 (PD-1) with Clinicopathological Characteristics of Renal Cell Carcinoma May Indicate Potential Targets for Treatment. Experiment 2018, 24, 6861–6872. [Google Scholar] [CrossRef]
- Triebel, F.; Jitsukawa, S.; Baixeras, E.; Roman-Roman, S.; Genevee, C.; Viegas-Pequignot, E.; Hercend, T. LAG-3, a novel lymphocyte activation gene closely related to CD4. J. Exp. Med. 1990, 171, 1393–1405. [Google Scholar] [CrossRef] [Green Version]
- Maruhashi, T.; Okazaki, I.-M.; Sugiura, D.; Takahashi, S.; Maeda, T.K.; Shimizu, K.; Okazaki, T. LAG-3 inhibits the activation of CD4+ T cells that recognize stable pMHCII through its conformation-dependent recognition of pMHCII. Nat. Immunol. 2018, 19, 1415–1426. [Google Scholar] [CrossRef]
- Huard, B.; Mastrangeli, R.; Prigent, P.; Bruniquel, D.; Donini, S.; El-Tayar, N.; Maigret, B.; Dréano, M.; Triebel, F. Characterization of the major histocompatibility complex class II binding site on LAG-3 protein. Proc. Natl. Acad. Sci. USA 1997, 94, 5744–5749. [Google Scholar] [CrossRef] [Green Version]
- Xu, F.; Liu, J.; Liu, D.; Liu, B.; Wang, M.; Hu, Z.; Du, X.; Tang, L.; He, F. LSECtin Expressed on Melanoma Cells Promotes Tumor Progression by Inhibiting Antitumor T-cell Responses. Cancer Res. 2014, 74, 3418–3428. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kouo, T.; Huang, L.; Pucsek, A.B.; Cao, M.; Solt, S.; Armstrong, T.; Jaffee, E. Galectin-3 Shapes Antitumor Immune Responses by Suppressing CD8+ T Cells via LAG-3 and Inhibiting Expansion of Plasmacytoid Dendritic Cells. Cancer Immunol. Res. 2015, 3, 412–423. [Google Scholar] [CrossRef] [Green Version]
- Wang, J.; Sanmamed, M.F.; Datar, I.; Su, T.T.; Ji, L.; Sun, J.; Chen, L.; Chen, Y.; Zhu, G.; Yin, W.; et al. Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3. Cell 2019, 176, 334–347.e12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wei, T.; Zhang, J.; Qin, Y.; Wu, Y.; Zhu, L.; Lu, L.; Tang, G.; Shen, Q. Increased expression of immunosuppressive molecules on intratumoral and circulating regulatory T cells in non-small-cell lung cancer patients. Am. J. Cancer Res. 2015, 5, 2190–2201. [Google Scholar] [PubMed]
- Andrews, L.P.; Marciscano, A.E.; Drake, C.G.; Vignali, D.A.A. LAG3 (CD223) as a cancer immunotherapy target. Immunol. Rev. 2017, 276, 80–96. [Google Scholar] [CrossRef] [Green Version]
- Zelba, H.; Bedke, J.; Hennenlotter, J.; Mostböck, S.; Zettl, M.; Zichner, T.; Chandran, P.A.; Stenzl, A.; Rammensee, H.-G.; Gouttefangeas, C. PD-1 and LAG-3 Dominate Checkpoint Receptor–Mediated T-cell Inhibition in Renal Cell Carcinoma. Cancer Immunol. Res. 2019, 7, 1891–1899. [Google Scholar] [CrossRef]
- Giraldo, N.A.; Becht, E.; Pagès, F.; Skliris, G.P.; Verkarre, V.; Vano, Y.; Mejean, A.; Saint-Aubert, N.; Lacroix, L.; Natario, I.; et al. Orchestration and Prognostic Significance of Immune Checkpoints in the Microenvironment of Primary and Metastatic Renal Cell Cancer. Clin. Cancer Res. 2015, 21, 3031–3040. [Google Scholar] [CrossRef] [Green Version]
- Li, N.; Wang, Y.; Forbes, K.; Vignali, K.M.; Heale, B.S.; Saftig, P.; Hartmann, D.; A Black, R.; Rossi, J.J.; Blobel, C.P.; et al. Metalloproteases regulate T-cell proliferation and effector function via LAG-3. EMBO J. 2007, 26, 494–504. [Google Scholar] [CrossRef] [Green Version]
- Möller-Hackbarth, K.; Dewitz, C.; Schweigert, O.; Trad, A.; Garbers, C.; Rose-John, S.; Scheller, J. A Disintegrin and Metalloprotease (ADAM) 10 and ADAM17 Are Major Sheddases of T Cell Immunoglobulin and Mucin Domain 3 (Tim-3). J. Biol. Chem. 2013, 288, 34529–34544. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Théate, I.; van Baren, N.; Pilotte, L.; Moulin, P.; Larrieu, P.; Renauld, J.-C.; Hervé, C.; Gutierrez-Roelens, I.; Marbaix, E.; Sempoux, C.; et al. Extensive Profiling of the Expression of the Indoleamine 2,3-Dioxygenase 1 Protein in Normal and Tumoral Human Tissues. Cancer Immunol. Res. 2015, 3, 161–172. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Metz, R.; Rust, S.; DuHadaway, J.B.; Mautino, M.R.; Munn, D.H.; Vahanian, N.N.; Link, C.J.; Prendergast, G.C. IDO inhibits a tryptophan sufficiency signal that stimulates mTOR: A novel IDO effector pathway targeted by D-1-methyl-tryptophan. Oncoimmunology 2012, 1, 1460–1468. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mezrich, J.D.; Fechner, J.H.; Zhang, X.; Johnson, B.P.; Burlingham, W.J.; Bradfield, C.A. An Interaction between Kynurenine and the Aryl Hydrocarbon Receptor Can Generate Regulatory T Cells. J. Immunol. 2010, 185, 3190–3198. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lines, J.L.; Pantazi, E.; Mak, J.; Sempere, L.F.; Wang, L.; O’Connell, S.; Ceeraz, S.; Suriawinata, A.A.; Yan, S.; Ernstoff, M.S.; et al. VISTA Is an Immune Checkpoint Molecule for Human T Cells. Cancer Res. 2014, 74, 1924–1932. [Google Scholar] [CrossRef] [Green Version]
- Huang, X.; Zhang, X.; Li, E.; Zhang, G.; Wang, X.; Tang, T.; Bai, X.; Liang, T. VISTA: An immune regulatory protein checking tumor and immune cells in cancer immunotherapy. J. Hematol. Oncol. 2020, 13, 83. [Google Scholar] [CrossRef]
- Hong, S.; Yuan, Q.; Xia, H.; Zhu, G.; Feng, Y.; Wang, Q.; Zhang, Z.; He, W.; Lu, J.; Dong, C.; et al. Analysis of VISTA expression and function in renal cell carcinoma highlights VISTA as a potential target for immunotherapy. Protein Cell 2019, 10, 840–845. [Google Scholar] [CrossRef] [Green Version]
- Roux, D.T.-L.; Sautreuil, M.; Bentriou, M.; Vérine, J.; Palma, M.B.; Daouya, M.; Bouhidel, F.; Lemler, S.; LeMaoult, J.; Desgrandchamps, F.; et al. Comprehensive landscape of immune-checkpoints uncovered in clear cell renal cell carcinoma reveals new and emerging therapeutic targets. Cancer Immunol. Immunother. 2020, 69, 1237–1252. [Google Scholar] [CrossRef]
- Yang, J.C.; Hughes, M.; Kammula, U.; Royal, R.; Sherry, R.M.; Topalian, S.L.; Suri, K.B.; Levy, C.; Allen, T.; Mavroukakis, S.; et al. Ipilimumab (Anti-CTLA4 Antibody) Causes Regression of Metastatic Renal Cell Cancer Associated With Enteritis and Hypophysitis. J. Immunother. 2007, 30, 825–830. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Motzer, R.J.; Escudier, B.; McDermott, D.F.; George, S.; Hammers, H.J.; Srinivas, S.; Tykodi, S.S.; Sosman, J.A.; Procopio, G.; Plimack, E.R.; et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N. Engl. J. Med. 2015, 373, 1803–1813. [Google Scholar] [CrossRef] [Green Version]
- Motzer, R.J.; Escudier, B.; George, S.; Hammers, H.J.; Srinivas, S.; Tykodi, S.S.; Sosman, J.A.; Plimack, E.R.; Procopio, G.; McDermott, D.F.; et al. Nivolumab versus everolimus in patients with advanced renal cell carcinoma: Updated results with long-term follow-up of the randomized, open-label, phase 3 CheckMate 025 trial. Cancer 2020, 126, 4156–4167. [Google Scholar] [CrossRef] [PubMed]
- Hammers, H.J.; Plimack, E.R.; Infante, J.R.; Rini, B.I.; McDermott, D.F.; Lewis, L.D.; Voss, M.H.; Sharma, P.; Pal, S.K.; Razak, A.R.A.; et al. Safety and Efficacy of Nivolumab in Combination With Ipilimumab in Metastatic Renal Cell Carcinoma: The CheckMate 016 Study. J. Clin. Oncol. 2017, 35, 3851–3858. [Google Scholar] [CrossRef] [Green Version]
- Motzer, R.J.; Tannir, N.M.; McDermott, D.F.; Aren Frontera, O.; Melichar, B.; Choueiri, T.K.; Plimack, E.R.; Barthélémy, P.; Porta, C.; George, S.; et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N. Engl. J. Med. 2018, 378, 1277–1290. [Google Scholar] [CrossRef] [PubMed]
- Albiges, L.; Tannir, N.M.; Burotto, M.; McDermott, D.; Plimack, E.R.; Barthélémy, P.; Porta, C.; Powles, T.; Donskov, F.; George, S.; et al. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: Extended 4-year follow-up of the phase III CheckMate 214 trial. ESMO Open 2020, 5, e001079. [Google Scholar] [CrossRef]
- McDermott, D.F.; Lee, J.-L.; Ziobro, M.; Suarez, C.; Langiewicz, P.; Matveev, V.B.; Wiechno, P.; Gafanov, R.A.; Tomczak, P.; Pouliot, F.; et al. Open-Label, Single-Arm, Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Non–Clear Cell Renal Cell Carcinoma. J. Clin. Oncol. 2021, 39, 1029–1039. [Google Scholar] [CrossRef] [PubMed]
- McDermott, D.F.; Huseni, M.A.; Atkins, M.B.; Motzer, R.J.; Rini, B.I.; Escudier, B.; Fong, L.; Joseph, R.W.; Pal, S.K.; Reeves, J.A.; et al. Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. Nat. Med. 2018, 24, 749–757. [Google Scholar] [CrossRef]
- Naing, A.; Gainor, J.F.; Gelderblom, H.; Forde, P.M.; O Butler, M.; Lin, C.-C.; Sharma, S.; de Olza, M.O.; Varga, A.; Taylor, M.; et al. A first-in-human phase 1 dose escalation study of spartalizumab (PDR001), an anti–PD-1 antibody, in patients with advanced solid tumors. J. Immunother. Cancer 2019, 8, e000530. [Google Scholar] [CrossRef] [Green Version]
- Motzer, R.J.; Powles, T.; Atkins, M.B.; Escudier, B.; McDermott, D.F.; Alekseev, B.Y.; Lee, J.-L.; Suarez, C.; Stroyakovskiy, D.; De Giorgi, U.; et al. Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma. JAMA Oncol. 2022, 8, 275. [Google Scholar] [CrossRef]
- Motzer, R.J.; Penkov, K.; Haanen, J.; Rini, B.; Albiges, L.; Campbell, M.T.; Venugopal, B.; Kollmannsberger, C.; Negrier, S.; Uemura, M.; et al. Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N. Engl. J. Med. 2019, 380, 1103–1115. [Google Scholar] [CrossRef]
- Powles, T.; Plimack, E.R.; Soulières, D.; Waddell, T.; Stus, V.; Gafanov, R.; Nosov, D.; Pouliot, F.; Melichar, B.; Vynnychenko, I.; et al. Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): Extended follow-up from a randomised, open-label, phase 3 trial. Lancet Oncol. 2020, 21, 1563–1573. [Google Scholar] [CrossRef]
- Motzer, R.; Alekseev, B.; Rha, S.-Y.; Porta, C.; Eto, M.; Powles, T.; Grünwald, V.; Hutson, T.E.; Kopyltsov, E.; Méndez-Vidal, M.J.; et al. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N. Engl. J. Med. 2021, 384, 1289–1300. [Google Scholar] [CrossRef]
- Choueiri, T.K.; Powles, T.; Burotto, M.; Escudier, B.; Bourlon, M.T.; Zurawski, B.; Oyervides Juárez, V.M.; Hsieh, J.J.; Basso, U.; Shah, A.Y.; et al. Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N. Engl. J. Med. 2021, 384, 829–841. [Google Scholar] [CrossRef]
- Msaouel, P. Less is More? First Impressions From COSMIC-313. Cancer Investig. 2022, 41, 101–106. [Google Scholar] [CrossRef]
- Brignone, C.; Escudier, B.; Grygar, C.; Marcu, M.; Triebel, F. A Phase I Pharmacokinetic and Biological Correlative Study of IMP321, a Novel MHC Class II Agonist, in Patients with Advanced Renal Cell Carcinoma. Clin. Cancer Res. 2009, 15, 6225–6231. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schoenfeld, D.A.; Merkin, R.D.; Moutafi, M.; Martinez, S.; Adeniran, A.; Kumar, D.; Jilaveanu, L.; Hurwitz, M.; Rimm, D.L.; Kluger, H.M. Location matters: LAG3 levels are lower in renal cell carcinoma metastatic sites compared to primary tumors, and expression at metastatic sites only may have prognostic importance. Front. Oncol. 2022, 12, 990367. [Google Scholar] [CrossRef]
- Curigliano, G.; Gelderblom, H.; Mach, N.; Doi, T.; Tai, D.; Forde, P.M.; Sarantopoulos, J.; Bedard, P.L.; Lin, C.-C.; Hodi, F.S.; et al. Phase I/Ib Clinical Trial of Sabatolimab, an Anti–TIM-3 Antibody, Alone and in Combination with Spartalizumab, an Anti–PD-1 Antibody, in Advanced Solid Tumors. Clin. Cancer Res. 2021, 27, 3620–3629. [Google Scholar] [CrossRef]
- Gutierrez, M.E.; Tang, S.-C.; Powderly, J.D.; Balmanoukian, A.S.; Janik, J.; Hoyle, P.; Wei, W.; Gong, X.; Hamid, O. 730MO First-in-human phase I study of INCAGN02390, a TIM-3 monoclonal antibody antagonist in patients with advanced malignancies. Ann. Oncol. 2022, 33, S876–S877. [Google Scholar] [CrossRef]
- Jung, K.H.; LoRusso, P.; Burris, H.; Gordon, M.; Bang, Y.-J.; Hellmann, M.D.; Cervantes, A.; de Olza, M.O.; Marabelle, A.; Hodi, F.S.; et al. Phase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced Solid Tumors. Clin. Cancer Res. 2019, 25, 3220–3228. [Google Scholar] [CrossRef] [Green Version]
- Tagliamento, M.; Agostinetto, E.; Borea, R.; Brandão, M.; Poggio, F.; Addeo, A.; Lambertini, M. VISTA: A Promising Target for Cancer Immunotherapy? ImmunoTargets Ther. 2021, 10, 185–200. [Google Scholar] [CrossRef] [PubMed]
- dos Reis, A.F.P.; Simão, D.; Odeny, T.; Rodrigues, C.; Fontes-Sousa, M.; da Luz, R.; Chowdry, R.P.; Welsh, S.J.; Paller, C.; Barata, P.C. A Systematic Review of Immune Checkpoint Inhibitors in Non-Clear-Cell Renal Cancer. Kidney Cancer 2022, 6, 115–127. [Google Scholar] [CrossRef] [PubMed]
- Koshkin, V.S.; Barata, P.C.; Zhang, T.; George, D.J.; Atkins, M.B.; Kelly, W.J.; Vogelzang, N.J.; Pal, S.K.; Hsu, J.; Appleman, L.J.; et al. Clinical activity of nivolumab in patients with non-clear cell renal cell carcinoma. J. Immunother. Cancer 2018, 6, 9. [Google Scholar] [CrossRef] [Green Version]
- Boilève, A.; Carlo, M.I.; Barthélémy, P.; Oudard, S.; Borchiellini, D.; Voss, M.H.; George, S.; Chevreau, C.; Landman-Parker, J.; Tabone, M.-D.; et al. Immune checkpoint inhibitors in MITF family translocation renal cell carcinomas and genetic correlates of exceptional responders. J. Immunother. Cancer 2018, 6, 159. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- de Vries-Brilland, M.; Gross-Goupil, M.; Seegers, V.; Boughalem, E.; Beuselinck, B.; Thibault, C.; Chevreau, C.; Ladoire, S.; Barthélémy, P.; Negrier, S.; et al. Are immune checkpoint inhibitors a valid option for papillary renal cell carcinoma? A multicentre retrospective study. Eur. J. Cancer 2020, 136, 76–83. [Google Scholar] [CrossRef] [PubMed]
- Keskin, S.K.; Msaouel, P.; Hess, K.R.; Yu, K.-J.; Matin, S.F.; Sircar, K.; Tamboli, P.; Jonasch, E.; Wood, C.G.; Karam, J.A.; et al. Outcomes of Patients with Renal Cell Carcinoma and Sarcomatoid Dedifferentiation Treated with Nephrectomy and Systemic Therapies: Comparison between the Cytokine and Targeted Therapy Eras. J. Urol. 2017, 198, 530–537. [Google Scholar] [CrossRef]
- Jones, J.O.; Ince, W.H.J.; Welsh, S.J.; Stewart, G.D. Activity of Immunotherapy Regimens on Primary Renal Tumours: A Systematic Review. Kidney Cancer 2022, 6, 221–236. [Google Scholar] [CrossRef]
- Gulati, S.; Lara, P.N. Immune Checkpoint Inhibitors in the Pre-operative Setting and Impact on the Primary Renal Tumor. Kidney Cancer 2022, 6, 201–203. [Google Scholar] [CrossRef] [PubMed]
Target | Drug | Clinical Trials |
---|---|---|
LAG-3 | IMP231 Relatlimab | NCT00351949 NCT05148546 |
TIM-3 | Sabatolimab INCAGN02390 | NCT02608268 NCT03652077 |
VISTA | CA-170 | NCT02812875 |
IDO1 | Navoximod | NCT02471846 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Lasorsa, F.; di Meo, N.A.; Rutigliano, M.; Milella, M.; Ferro, M.; Pandolfo, S.D.; Crocetto, F.; Tataru, O.S.; Autorino, R.; Battaglia, M.; et al. Immune Checkpoint Inhibitors in Renal Cell Carcinoma: Molecular Basis and Rationale for Their Use in Clinical Practice. Biomedicines 2023, 11, 1071. https://doi.org/10.3390/biomedicines11041071
Lasorsa F, di Meo NA, Rutigliano M, Milella M, Ferro M, Pandolfo SD, Crocetto F, Tataru OS, Autorino R, Battaglia M, et al. Immune Checkpoint Inhibitors in Renal Cell Carcinoma: Molecular Basis and Rationale for Their Use in Clinical Practice. Biomedicines. 2023; 11(4):1071. https://doi.org/10.3390/biomedicines11041071
Chicago/Turabian StyleLasorsa, Francesco, Nicola Antonio di Meo, Monica Rutigliano, Martina Milella, Matteo Ferro, Savio Domenico Pandolfo, Felice Crocetto, Octavian Sabin Tataru, Riccardo Autorino, Michele Battaglia, and et al. 2023. "Immune Checkpoint Inhibitors in Renal Cell Carcinoma: Molecular Basis and Rationale for Their Use in Clinical Practice" Biomedicines 11, no. 4: 1071. https://doi.org/10.3390/biomedicines11041071