Boosting the Immune Response with the Combination of Electrochemotherapy and Immunotherapy: A New Weapon for Squamous Cell Carcinoma of the Head and Neck?
Abstract
:Simple Summary
Abstract
1. Background
2. Electrochemotherapy
3. Boosting the Immune Response against Cancer: Biological Mechanisms and Data from the Literature
4. The Landscape of Immuno-ECT in SCCHN
5. Discussions and Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018, 68, 394. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gillison, M.L.; Chaturvedi, A.K.; Anderson, W.F.; Fakhry, C. Epidemiology of Human Papillomavirus–Positive Head and Neck Squamous Cell Carcinoma. J. Clin. Oncol. 2015, 33, 3235–3242. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cognetti, D.M.; Weber, R.S.; Lai, S.Y. Head and Neck Cancer: An Evolving Treatment Paradigm. Cancer 2008, 113, 1911–1932. [Google Scholar] [CrossRef] [PubMed]
- Caponigro, F.; Ionna, F.; Scarpati, G.D.V.; Longo, F.; Addeo, R.; Manzo, R.; Muto, P.; Pisconti, S.; Leopaldi, L.; Perri, F. Translational Research: A Future Strategy for Managing Squamous Cell Carcinoma of the Head and Neck? Anticancer Agents Med. Chem. 2018, 18, 1220–1227. [Google Scholar] [CrossRef]
- Perri, F.; Ionna, F.; Muto, P.; Di Marzo, M.; Caponigro, F.; Longo, F.; Scarpati, G.D.V.; Di Lorenzo, G.; Giuliano, M.; Solla, R. Genetics and management of locally advanced carcinomas of the head and neck: Role of altered fractionation radiotherapy. Future Sci. OA 2018, 5, FSO347. [Google Scholar] [CrossRef] [Green Version]
- Chang, J.; Wu, C.C.; Yuan, K.S.; Wu, A.T.H.; Wu, S.Y. Locoregionally recurrent head and neck squamous cell carcinoma: Incidence, survival, prognostic factors, and treatment outcomes. Oncotarget 2017, 8, 55600–55612. [Google Scholar] [CrossRef] [Green Version]
- Wiegand, S.; Zimmermann, A.; Wilhelm, T.; Werner, J.A. Survival After Distant Metastasis in Head and Neck Cancer. Anticancer Res. 2015, 35, 5499–5502. [Google Scholar]
- Ward, E.; Smith, R.; Branca, J.J.; Noakes, D.; Morucci, G.; Thyer, L. Clinical experience of cancer immunotherapy integrated with Oleic Acid complexed with de-glycosylated vitamin D binding protein. Am. J. Immunol. 2014, 10, 23–32. [Google Scholar] [CrossRef] [Green Version]
- Liu, C.; Yang, H.; Zhang, R.; Zhao, J.J.; Hao, D. Tumour-associated antigens and their anti-cancer applications. Eur. J. Cancer Care 2016, 26, e12446. [Google Scholar] [CrossRef]
- Jackson, S.R.; Yuan, J.; Teague, R.M. Targeting CD8+ T-cell tolerance for cancer immunotherapy. Immunotherapy 2014, 6, 833–852. [Google Scholar] [CrossRef] [Green Version]
- Wherry, E.J.; Kurachi, M. Molecular and cellular insights into T cell exhaustion. Nat. Rev. Immunol. 2015, 15, 486–499. [Google Scholar] [CrossRef] [PubMed]
- Alsaab, H.O.; Sau, S.; Alzhrani, R.; Tatiparti, K.; Bhise, K.; Kashaw, S.K.; Iyer, A.K. PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome. Front. Pharmacol. 2017, 8, 561. [Google Scholar] [CrossRef]
- Philips, G.K.; Atkins, M. Therapeutic uses of anti-PD-1 and anti-PD-L1 antibodies. Int. Immunol. 2015, 27, 39–46. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Honeychurch, J.; Cheadle, E.J.; Dovedi, S.J.; Illidge, T.M. Immuno-regulatory antibodies for the treatment of cancer. Expert Opin. Biol. Ther. 2015, 15, 787–801. [Google Scholar] [CrossRef] [PubMed]
- Gehl, J.; Skovsgaard, T.; Mir, L.M. Enhancement of cytotoxicity by electropermeabilization: An improved method for screening drugs. Anticancer Drugs 1998, 9, 319–325. [Google Scholar] [CrossRef]
- Mir, L.M.; Glass, L.F.; Sersa, G.; Teissié, J.; Domenge, C.; Miklavcic, D.; Jaroszeski, M.J.; Orlowski, S.; Reintgen, D.S.; Rudolf, Z.; et al. Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy. Br. J. Cancer 1998, 77, 2336–2342. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Calvet, C.Y.; Mir, L.M. The promising alliance of anti-cancer electrochemotherapy with immunotherapy. Cancer Metastasis Rev. 2016, 35, 165–177. [Google Scholar] [CrossRef] [Green Version]
- Jarm, T.; Cemazar, M.; Miklavcic, D.; Sersa, G. Antivascular effects of electrochemotherapy: Implications in treatment of bleeding metastases. Expert Rev. Anticancer Ther. 2010, 10, 729–746. [Google Scholar] [CrossRef]
- Rotunno, R.; Campana, L.G.; Quaglino, P.; de Terlizzi, F.; Kunte, C.; Odili, J.; Gehl, J.; Ribero, S.; Liew, S.H.; Marconato, R.; et al. Electrochemotherapy of unresectable cutaneous tumours with reduced dosages of intravenous bleomycin: Analysis of 57 patients from the International Network for Sharing Practices of Electrochemotherapy registry. J. Eur. Acad. Dermatol. Venereol. 2018, 32, 1147–1154. [Google Scholar] [CrossRef]
- Pichi, B.; Pellini, R.; Spriano, G. Electrochemotherapy—A locoregional therapy with well-established palliative effect in patient with large recurrent lesion of head and neck. J. Craniomaxillofac. Surg. 2019, 47, 41–46. [Google Scholar] [CrossRef]
- Mir, L.M.; Orlowski, S.; Poddevin, B.; Belehradek, J., Jr. Electrochemotherapy tumor treatment is improved by interleukin-2 stimulation of the host’s defenses. Eur. Cytokine Netw. 1992, 3, 331–334. [Google Scholar] [PubMed]
- Sersa, G.; Miklavcic, D.; Cemazar, M.; Belehradek, J.; Jarm, T.; Mir, L.M. Electrochemotherapy with CDDP on LPB sarcoma: Comparison of the anti-tumor effectiveness in immunocompetent and immunodeficient mice. Bioelectrochem. Bioenerg. 1997, 43, 279–283. [Google Scholar] [CrossRef]
- Mir, L.M.; Orlowski, S.; Belehradek, J., Jr.; Paoletti, C. Electrochemotherapy potentiation of antitumour effect of bleomycin by local electric pulses. Eur. J. Cancer 1991, 27, 68–72. [Google Scholar] [CrossRef]
- Mir, L.M.; Roth, C.; Orlowski, S.; Belehradek, J., Jr.; Fradelizi, D.; Paoletti, C.; Kourilsky, P. Potentiation of the antitumoral effect of electrochemotherapy by immunotherapy with allogeneic cells producing interleukin 2. C. R. Acad. Sci. III 1992, 314, 539–544. [Google Scholar] [PubMed]
- Gerlini, G.; Sestini, S.; Di Gennaro, P.; Urso, C.; Pimpinelli, N.; Borgognoni, L. Dendritic cells recruitment in melanoma metastasis treated by electrochemotherapy. Clin. Exp. Metastasis 2013, 30, 37–45. [Google Scholar] [CrossRef]
- Roux, S.; Bernat, C.; Al-Sakere, B.; Ghiringhelli, F.; Opolon, P.; Carpentier, A.F.; Zitvogel, L.; Mir, L.M.; Robert, C. Tumor destruction using electrochemotherapy followed by CpG oligodeoxynucleotide injection induces distant tumor responses. Cancer Immunol. Immunother. 2008, 57, 1291–1300. [Google Scholar] [CrossRef]
- Calvet, C.Y.; Famin, D.; Andre, F.M.; Mir, L.M. Electrochemotherapy with bleomycin induces hallmarks of immunogenic cell death in murine colon cancer cells. Oncoimmunology 2014, 3, e28131. [Google Scholar] [CrossRef] [Green Version]
- Kroemer, G.; Galluzzi, L.; Kepp, O.; Zitvogel, L. Immunogenic cell death in cancer therapy. Ann. Rev. Immunol. 2013, 31, 51–72. [Google Scholar] [CrossRef]
- Ledur, P.F.; Villodre, E.S.; Paulus, R.; Cruz, L.A.; Flores, D.G.; Lenz, G. Extracellular ATP reduces tumor sphere growth and cancer stem cell population in glioblastoma cells. Purinergic Signal. 2012, 8, 39–48. [Google Scholar] [CrossRef] [Green Version]
- Inoda, S.; Hirohashi, Y.; Torigoe, T.; Morita, R.; Takahashi, A.; Asanuma, H.; Nakatsugawa, M.; Nishizawa, S.; Tamura, Y.; Tsuruma, T.; et al. Cytotoxic T lymphocytes efficiently recognize human colon cancer stem-like cells. Am. J. Pathol. 2011, 178, 1805–1813. [Google Scholar] [CrossRef]
- Falk, H.; Forde, P.F.; Bay, M.L.; Mangalanathan, U.M.; Hojman, P.; Soden, D.M.; Gehl, J. Calcium electroporation induces tumor eradication, long-lasting immunity and cytokine responses in the CT26 colon cancer mouse model. Oncoimmunology 2017, 6, e1301332. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gunji, Y.; Uesato, M.; Miyazaki, S.; Shimada, H.; Matsubara, H.; Nabeya, Y.; Kouda, K.; Makino, H.; Kouzu, T.; Ochiai, T. Generation of antitumor immunity against large colon tumors by repeated runs of electrochemotherapy. Hepatogastroenterology 2005, 52, 770–774. [Google Scholar] [PubMed]
- Goggins, C.A.; Khachemoune, A. The use of electrochemotherapy in combination with immunotherapy in the treatment of metastatic melanoma: A focused review. Int. J. Dermatol. 2019, 58, 865–870. [Google Scholar] [CrossRef] [PubMed]
- Mir, L.M.; Roth, C.; Orlowski, S.; Quintin-Colonna, F.; Fradelizi, D.; Belehradek, J.; Kourilsky, P. Systemic antitumor effects of electrochemotherapy combined with histoincompatible cells secreting interleukin-2. J. Immunother. Emphas. Tumor Immunol. 1995, 17, 30–38. [Google Scholar] [CrossRef] [PubMed]
- Brizio, M.; Fava, P.; Astrua, C.; Cavaliere, G.; Savoia, P. Complete regression of melanoma skin metastases after electrochemotherapy plus ipilimumab treatment: An unusual clinical presentation. Eur. J. Dermatol. 2015, 25, 271–272. [Google Scholar] [CrossRef] [PubMed]
- Mozzillo, N.; Simeone, E.; Benedetto, L.; Curvietto, M.; Giannarelli, D.; Gentilcore, G.; Camerlingo, R.; Capone, M.; Madonna, G.; Festino, L.; et al. Assessing a novel immuno-oncology-based combination therapy: Ipilimumab plus electrochemotherapy. Oncoimmunology 2015, 4, e1008842. [Google Scholar] [CrossRef]
- Karaca, B.; Yayla, G.; Erdem, M.; Gürler, T. Electrochemotherapy with anti-PD-1 treatment induced durable complete response in heavily pretreated metastatic melanoma patient. Anticancer Drugs 2017, 29, 190–196. [Google Scholar] [CrossRef]
- Heppt, M.V.; Eigentler, T.K.; Kahler, K.C.; Herbst, R.A.; Göppner, D.; Gambichler, T.; Ulrich, J.; Dippel, E.; Loquai, C.; Schell, B. Immune checkpoint blockade with concurrent electrochemotherapy in advanced melanoma: A retrospective multicenter analysis. Cancer Immunol. Immunother. 2016, 65, 951–959. [Google Scholar] [CrossRef]
- Mir, L.M.; Gehl, J.; Sersa, G.; Collins, C.G.; Garbay, J.R.; Billard, V.; Geertsen, P.F.; Rudolf, Z.; O’Sullivan, G.C.; Marty, M. Standard operating procedures of the electrochemotherapy: Instructions for the use of bleomycin or cisplatin administered either systemically or locally and electric pulses delivered means of invasive or non-invasive electrodes. Eur. J. Cancer Suppl. 2006, 4, 14–25. [Google Scholar] [CrossRef]
- Gehl, J.; Sersa, G.; Matthiessen, L.W.; Muir, T.; Soden, D.; Occhini, A.; Quaglino, P.; Curatolo, P.; Campana, L.G.; Kunte, C.; et al. Updated standard operating procedures for electrochemotherapy of cutaneous tumours and skin metastases. Acta Oncol. 2018, 25, 1–9. [Google Scholar] [CrossRef]
- Bertino, G.; Sersa, G.; De Terlizzi, F.; Occhini, A.; Plaschke, C.C.; Groselj, A.; Langdon, C.; Grau, J.J.; McCaul, J.A.; Heuveling, D.; et al. European Research on Electrochemotherapy in Head and Neck Cancer (EURECA) project: Results of the treatment of skin cancer. Eur. J. Cancer 2016, 63, 41–52. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Eric, W.; Chika, A.; Brandon, M.; John, Y.; Kelvin, C. Systemic therapy in the curative treatment of head and neck squamous cell cancer: A systematic review. J. Otolaryngol. Head Neck Surg. 2017, 46, 29. [Google Scholar]
- Lenzi, R.; Muscatello, L.; Saibene, A.M.; Felisati, G.; Pipolo, C.; Pipolo, C. The Controversial Role of Electrochemotherapy in Head and Neck Cancer: A Systematic Review of the Literature. Eur. Arch. Otorhinolaryngol. 2017, 274, 2389–2394. [Google Scholar] [CrossRef] [PubMed]
- Landström, F.J.; Reizenstein, J.; Adamsson, G.B.; Von Beckerath, M.; Möller, C. Long-term Follow-Up in Patients Treated with Curative Electrochemotherapy for Cancer in the Oral Cavity and Oropharynx. Acta Otolaryngol. 2015, 135, 1070–1078. [Google Scholar] [CrossRef] [PubMed]
- Longo, F.; Perri, F.; Pavone, E.; Aversa, C.; Maglione, M.G.; Guida, A.; Montano, M.; Villano, S.; Daponte, A.; Caponigro, F.; et al. Electrochemotherapy as palliative treatment in patients with advanced head and neck tumours: Outcome analysis in 93 patients treated in a single institution. Oral Oncol. 2019, 92, 77–84. [Google Scholar] [CrossRef]
- Ferris, R.L.; Blumenschein, G., Jr.; Fayette, J.; Guigay, J.; Colevas, A.D.; Licitra, L.; Harrington, K.; Kasper, S.; Vokes, E.E.; Even, C.; et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N. Engl. J. Med. 2016, 375, 1856–1867. [Google Scholar] [CrossRef]
- Cohen, E.E.W.; Soulières, D.; Le Tourneau, C.; Dinis, J.; Licitra, L.; Ahn, M.J.; Soria, A.; Machiels, J.-P.; Mach, N.; Mehra, R.; et al. KEYNOTE-040 investigators. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): A randomised, open-label, phase 3 study. Lancet 2019, 393, 156–167. [Google Scholar]
- Saâda-Bouzid, E.; Defaucheux, C.; Karabajakian, A.; Coloma, V.P.; Servois, V.; Paoletti, X.; Even, C.; Fayette, J.; Guigay, J.; Loirat, D.; et al. Hyperprogression During anti-PD-1/PD-L1 Therapy in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma. Ann. Oncol. 2017, 28, 1605–1611. [Google Scholar] [CrossRef]
- Theurich, S.; Rothschild, S.I.; Hoffmann, M.; Fabri, M.; Sommer, A.; Garcia-Marquez, M.; Thelen, M.; Schill, C.; Merki, R.; Schmid, T.; et al. Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma. Cancer Immunol. Res. 2016, 4, 744–754. [Google Scholar] [CrossRef] [Green Version]
- Bonadies, A.; Bertozzi, E.; Cristiani, R.; Govoni, F.A.; Migliano, E. Electrochemotherapy in Skin Malignancies of Head and Neck Cancer Patients: Clinical Efficacy and Aesthetic Benefits. Acta Derm. Venereol. 2019, 99, 1246–1252. [Google Scholar] [CrossRef]
- Plaschke, C.C.; Johannesen, H.H.; Hansen, R.H.; Hendel, H.W.; Kiss, K.; Gehl, J.; Wessel, I. The DAHANCA 32 Study: Electrochemotherapy for Recurrent Mucosal Head and Neck Cancer. Head Neck 2019, 41, 329–339. [Google Scholar] [CrossRef] [PubMed]
- Plaschke, C.C.; Bertino, G.; McCaul, J.A.; Grau, J.J.; De Bree, R.; Sersa, G.; Occhini, A.; Groselj, A.; Langdon, C.; Heuveling, D.; et al. European Research on Electrochemotherapy in Head and Neck Cancer (EURECA) Project: Results from the Treatment of Mucosal Cancers. Eur. J. Cancer 2017, 87, 172–181. [Google Scholar] [CrossRef] [PubMed]
- Di Monta, G.; Caracó, C.; Simeone, E.; Grimaldi, A.M.; Marone, U.; Di Marzo, M.; Vanella, V.; Festino, L.; Palla, M.; Mori, S.; et al. Electrochemotherapy Efficacy Evaluation for Treatment of Locally Advanced Stage III Cutaneous Squamous Cell Carcinoma: A 22-cases Retrospective Analysis. J. Transl. Med. 2017, 15, 82. [Google Scholar] [CrossRef] [PubMed]
- Gargiulo, M.; Papa, A.; Capasso, P.; Moio, M.; Cubicciotti, E.; Parascandolo, S. Electrochemotherapy for Non-Melanoma Head and Neck Cancers: Clinical Outcomes in 25 Patients. Ann. Surg. 2012, 255, 1158–1164. [Google Scholar] [CrossRef]
- Landström, F.J.; Nilsson, C.O.; Crafoord, S.; Reizenstein, J.A.; Adamsson, G.B.; Löfgren, L.A. Electroporation Therapy of Skin Cancer in the Head and Neck Area. Dermatol. Surg. 2010, 36, 1245–1250. [Google Scholar] [CrossRef]
- Trommer, M.; Yeo, S.Y.; Persigehl, T.; Bunck, A.; Grüll, H.; Schlaak, M.; Theurich, S.; Von Bergwelt-Baildon, M.; Morgenthaler, J.; Herter, J.M.; et al. Abscopal Effects in Radio-Immunotherapy-Response Analysis of Metastatic Cancer Patients With Progressive Disease Under Anti-PD-1 Immune Checkpoint Inhibition. Front. Pharmacol. 2019, 10, 511. [Google Scholar] [CrossRef] [Green Version]
- Mandal, R.; Şenbabaoğlu, Y.; Desrichard, A.; Havel, J.J.; Dalin, M.; Riaz, N.; Lee, K.-W.; Ganly, I.; Hakimi, A.A.; Chan, T.; et al. The head and neck cancer immune landscape and its immunotherapeutic implications. JCI Insight 2016, 1, e89829. [Google Scholar] [CrossRef] [Green Version]
- Alexandrov, L.B.; Initiative, A.P.C.G.; Nik-Zainal, S.; Wedge, D.C.; Aparicio, S.A.J.R.; Behjati, S.; Biankin, A.V.; Bignell, G.R.; Bolli, N.; Borg, A.; et al. Signatures of mutational processes in human cancer. Nature 2013, 500, 415–421. [Google Scholar] [CrossRef] [Green Version]
- Burtness, B.; Harrington, K.J.; Greil, R.; Soulières, D.; Tahara, M.; De Castro, G.; Psyrri, A.; Basté, N.; Neupane, P.; Bratland, Å.; et al. Pembrolizumab Alone or With Chemotherapy Versus Cetuximab With Chemotherapy for Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (KEYNOTE-048): A Randomised, Open-Label, Phase 3 Study. Lancet 2019, 394, 1915–1928. [Google Scholar] [CrossRef]
- Lee, K.A.; Shaw, H.M.; Bataille, V.; Nathan, P.; Spector, T.D. Role of the gut microbiome for cancer patients receiving immunotherapy: Dietary and treatment implications. Eur. J. Cancer 2020, 138, 149–155. [Google Scholar] [CrossRef]
- Routy, B.; Le Chatelier, E.; Derosa, L.; Duong, C.; Alou, M.T.; Daillère, R.; Fluckiger, A.; Messaoudene, M.; Rauber, C.; Roberti, M.P.; et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 2018, 359, 91e7. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gopalakrishnan, V.; Spencer, C.N.; Nezi, L.; Reuben, A.; Andrews, M.; Karpinets, T. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 2018, 359, 97–103. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- McQuade, J.L.; Daniel, C.R.; Helmink, B.A.; Wargo, J.A. Modulating the microbiome to improve therapeutic response in cancer. Lancet Oncol. 2019, 20, e77–e91. [Google Scholar] [CrossRef]
Published Paper | Target | Treatment | Type of Study | Number of Patients | Responses (ORR) |
---|---|---|---|---|---|
Oncoimmunology 2015; 4: e1008842. Mozzillo et al. [36] | Advanced Melanoma | ECT + ipilimumab | Retrospective trial | 15 | 67% |
Anticancer Drugs 2017; 29: 190–196. Karaca et al. [20] | Advanced Melanoma | ECT + nivolumab | Case report | 1 | Not Applicable |
Eur J Dermatol 2015; 25: 271–272. Brizio et al. [35] | Advanced Melanoma | ECT + ipilimumab | Case report | 1 | Not Applicable |
Cancer Immunol Immunother 2016; 65: 951–959. Heppt et al. [38] | Advanced Melanoma | ECT + ipilimumab vs. ECT + anti-PD-1 | Retrospective trial | 33 | 59.2% adding the values obtained in the two arms |
Published Papers | Target | Treatment | Type of Study | Number of Patients | Responses (ORR) |
---|---|---|---|---|---|
Acta Derm Venereol | Skin cancer | ECT | Retrospective trial | 33 | 100% |
2019. 1; 99(13): 1246–1252. | |||||
Bonadies et al. [50] | |||||
Head Neck 2019; 41(2): 329–339. | SCCHN | ECT | Phase II | 26 | 58% |
Plaschke et al. [51] | |||||
Eur J Cancer 2017 Dec; 87: 172–181. | SCCHN | ECT | Phase II | 36 | 56% |
Plaschke et al. [52] | |||||
J Transl Med 2017 Apr 26;15(1):82. | Skin cancer | ECT | Retrospective trial | 22 | 81.8% |
Di Monta et al. [53] | |||||
Ann Surg 2012 Jun;255(6):1158–64. | Skin cancer | ECT | Phase II trial | 25 | 100% |
Gargiulo et al. [54] | |||||
Oral Oncol. 2019 May; 92: 77–84. | SCCHN and Skin cancer | ECT | Retrospective trial | 93 | 45% |
Longo et al. [45] | |||||
Dermatol Surg. 2010 Aug; 36(8): 1245–50. | Skin cancer | ECT | Retrospective trial | 6 | 83% |
Landstrom et al. [55] |
© 2020 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 (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Longo, F.; Perri, F.; Caponigro, F.; Della Vittoria Scarpati, G.; Guida, A.; Pavone, E.; Aversa, C.; Muto, P.; Giuliano, M.; Ionna, F.; et al. Boosting the Immune Response with the Combination of Electrochemotherapy and Immunotherapy: A New Weapon for Squamous Cell Carcinoma of the Head and Neck? Cancers 2020, 12, 2781. https://doi.org/10.3390/cancers12102781
Longo F, Perri F, Caponigro F, Della Vittoria Scarpati G, Guida A, Pavone E, Aversa C, Muto P, Giuliano M, Ionna F, et al. Boosting the Immune Response with the Combination of Electrochemotherapy and Immunotherapy: A New Weapon for Squamous Cell Carcinoma of the Head and Neck? Cancers. 2020; 12(10):2781. https://doi.org/10.3390/cancers12102781
Chicago/Turabian StyleLongo, Francesco, Francesco Perri, Francesco Caponigro, Giuseppina Della Vittoria Scarpati, Agostino Guida, Ettore Pavone, Corrado Aversa, Paolo Muto, Mario Giuliano, Franco Ionna, and et al. 2020. "Boosting the Immune Response with the Combination of Electrochemotherapy and Immunotherapy: A New Weapon for Squamous Cell Carcinoma of the Head and Neck?" Cancers 12, no. 10: 2781. https://doi.org/10.3390/cancers12102781