LL-37 as a Powerful Molecular Tool for Boosting the Performance of Ex Vivo-Produced Human Dendritic Cells for Cancer Immunotherapy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Specimens
2.2. Preparation of Immature-Monocyte-Derived DCs
2.3. Pulsation and Maturation of Immature-Monocyte-Derived DCs
2.4. DC Maturation Analysis
2.5. DC-Induced Stimulation of Autologous Lymphocytes
2.6. Determination of the Tumor-Cell-Reactive T Cells in Cultured DC-Induced Autologous Lymphocytes
2.7. Evaluation of the Tumor Cell Co-Culture with DC-Induced Autologous Lymphocytes
2.8. Statistical Analysis
3. Results
3.1. LL-37 Was Important for Both DC Differentiation and Pulsation to Enhance DC-Mediated Expansion of CD8+ T Cells with Downregulated Expression of PD-1
3.2. LL-37 Was Important for DC Differentiation, Maturation, and Pulsation to Enhance DC-Mediated Expansion of Tumor-Cell-Specific CD8+ T Cells
3.3. LL-37 Did Not Enhance the Maturation of the Antigen-Pulsed DCs
3.4. LL-37-Treatment of DCs Resulted in the Production of T Cells with Superior Efficacy against Tumor Cells In Vitro
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Papaioannou, N.E.; Beniata, O.V.; Vitsos, P.; Tsitsilonis, O.; Samara, P. Harnessing the immune system to improve cancer therapy. Ann. Transl. Med. 2016, 4, 261. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bol, K.F.; Schreibelt, G.; Gerritsen, W.R.; de Vries, I.J.; Figdor, C.G. Dendritic Cell-Based Immunotherapy: State of the Art and Beyond. Clin. Cancer Res. 2016, 22, 1897–1906. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Amigorena, S. Dendritic Cells on the Way to Glory. J. Immunol. 2018, 200, 885–886. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Thordardottir, S.; Schaap, N.; Louer, E.; Kester, M.G.; Falkenburg, J.H.; Jansen, J.; Radstake, T.R.; Hobo, W.; Dolstra, H. Hematopoietic stem cell-derived myeloid and plasmacytoid DC-based vaccines are highly potent inducers of tumor-reactive T cell and NK cell responses ex vivo. Oncoimmunology 2017, 6, e1285991. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huber, A.; Dammeijer, F.; Aerts, J.; Vroman, H. Current State of Dendritic Cell-Based Immunotherapy: Opportunities for in vitro Antigen Loading of Different DC Subsets? Front. Immunol. 2018, 9, 2804. [Google Scholar] [CrossRef]
- Garg, A.D.; Vara Perez, M.; Schaaf, M.; Agostinis, P.; Zitvogel, L.; Kroemer, G.; Galluzzi, L. Trial watch: Dendritic cell-based anticancer immunotherapy. Oncoimmunology 2017, 6, e1328341. [Google Scholar] [CrossRef]
- Yang, L.; Shi, P.; Zhao, G.; Xu, J.; Peng, W.; Zhang, J.; Zhang, G.; Wang, X.; Dong, Z.; Chen, F.; et al. Targeting cancer stem cell pathways for cancer therapy. Signal Transduct. Target. Ther. 2020, 5, 8. [Google Scholar] [CrossRef] [Green Version]
- Fucikova, J.; Podrazil, M.; Jarolim, L.; Bilkova, P.; Hensler, M.; Becht, E.; Gasova, Z.; Klouckova, J.; Kayserova, J.; Horvath, R.; et al. Phase I/II trial of dendritic cell-based active cellular immunotherapy with DCVAC/PCa in patients with rising PSA after primary prostatectomy or salvage radiotherapy for the treatment of prostate cancer. Cancer Immunol. Immunother. CII 2018, 67, 89–100. [Google Scholar] [CrossRef]
- Podrazil, M.; Horvath, R.; Becht, E.; Rozkova, D.; Bilkova, P.; Sochorova, K.; Hromadkova, H.; Kayserova, J.; Vavrova, K.; Lastovicka, J.; et al. Phase I/II clinical trial of dendritic-cell based immunotherapy (DCVAC/PCa) combined with chemotherapy in patients with metastatic, castration-resistant prostate cancer. Oncotarget 2015, 6, 18192–18205. [Google Scholar] [CrossRef] [Green Version]
- Antonarakis, E.S.; Small, E.J.; Petrylak, D.P.; Quinn, D.I.; Kibel, A.S.; Chang, N.N.; Dearstyne, E.; Harmon, M.; Campogan, D.; Haynes, H.; et al. Antigen-Specific CD8 Lytic Phenotype Induced by Sipuleucel-T in Hormone-Sensitive or Castration-Resistant Prostate Cancer and Association with Overall Survival. Clin. Cancer Res. 2018, 24, 4662–4671. [Google Scholar] [CrossRef]
- Zhang, K.; Guo, Y.; Wang, X.; Zhao, H.; Ji, Z.; Cheng, C.; Li, L.; Fang, Y.; Xu, D.; Zhu, H.H.; et al. WNT/beta-Catenin Directs Self-Renewal Symmetric Cell Division of hTERT(high) Prostate Cancer Stem Cells. Cancer Res. 2017, 77, 2534–2547. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Khurana, N.; Sikka, S.C. Interplay Between SOX9, Wnt/beta-Catenin and Androgen Receptor Signaling in Castration-Resistant Prostate Cancer. Int. J. Mol. Sci. 2019, 20, 2066. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, Z.; Yu, W.; Zheng, M.; Liao, X.; Wang, J.; Yang, D.; Lu, W.; Wang, L.; Zhang, S.; Liu, H.; et al. Pin1 inhibition potently suppresses gastric cancer growth and blocks PI3K/AKT and Wnt/beta-catenin oncogenic pathways. Mol. Carcinog. 2019, 58, 1450–1464. [Google Scholar] [CrossRef] [PubMed]
- Geduk, A.; Atesoglu, E.B.; Tarkun, P.; Mehtap, O.; Hacihanefioglu, A.; Demirsoy, E.T.; Baydemir, C. The Role of beta-Catenin in Bcr/Abl Negative Myeloproliferative Neoplasms: An Immunohistochemical Study. Clin. Lymphoma Myeloma Leuk. 2015, 15, 785–789. [Google Scholar] [CrossRef]
- Kandler, K.; Shaykhiev, R.; Kleemann, P.; Klescz, F.; Lohoff, M.; Vogelmeier, C.; Bals, R. The anti-microbial peptide LL-37 inhibits the activation of dendritic cells by TLR ligands. Int. Immunol. 2006, 18, 1729–1736. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Davidson, D.J.; Currie, A.J.; Reid, G.S.; Bowdish, D.M.; MacDonald, K.L.; Ma, R.C.; Hancock, R.E.; Speert, D.P. The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization. J. Immunol. 2004, 172, 1146–1156. [Google Scholar] [CrossRef] [Green Version]
- Findlay, E.G.; Currie, A.J.; Zhang, A.; Ovciarikova, J.; Young, L.; Stevens, H.; McHugh, B.J.; Canel, M.; Gray, M.; Milling, S.W.F.; et al. Exposure to the antimicrobial peptide LL-37 produces dendritic cells optimized for immunotherapy. Oncoimmunology 2019, 8, 1608106. [Google Scholar] [CrossRef] [Green Version]
- Taborska, P.; Stakheev, D.; Svobodova, H.; Strizova, Z.; Bartunkova, J.; Smrz, D. Acute Conditioning of Antigen-Expanded CD8(+) T Cells via the GSK3beta-mTORC Axis Differentially Dictates Their Immediate and Distal Responses after Antigen Rechallenge. Cancers 2020, 12, 3766. [Google Scholar] [CrossRef]
- Kaighn, M.E.; Narayan, K.S.; Ohnuki, Y.; Lechner, J.F.; Jones, L.W. Establishment and characterization of a human prostatic carcinoma cell line (PC-3). Investig. Urol. 1979, 17, 16–23. [Google Scholar]
- Taborska, P.; Lastovicka, J.; Stakheev, D.; Strizova, Z.; Bartunkova, J.; Smrz, D. SARS-CoV-2 spike glycoprotein-reactive T cells can be readily expanded from COVID-19 vaccinated donors. Immun. Inflamm. Dis. 2021, 9, 1452–1467. [Google Scholar] [CrossRef]
- Stakheev, D.; Taborska, P.; Strizova, Z.; Podrazil, M.; Bartunkova, J.; Smrz, D. The WNT/beta-catenin signaling inhibitor XAV939 enhances the elimination of LNCaP and PC-3 prostate cancer cells by prostate cancer patient lymphocytes in vitro. Sci. Rep. 2019, 9, 4761. [Google Scholar] [CrossRef] [PubMed]
- Salah, A.; Wang, H.; Li, Y.; Ji, M.; Ou, W.B.; Qi, N.; Wu, Y. Insights Into Dendritic Cells in Cancer Immunotherapy: From Bench to Clinical Applications. Front. Cell Dev. Biol. 2021, 9, 686544. [Google Scholar] [CrossRef] [PubMed]
- Lak, S.; Janelle, V.; Djedid, A.; Boudreau, G.; Brasey, A.; Lisi, V.; Smaani, A.; Carli, C.; Busque, L.; Lavallee, V.P.; et al. Combined PD-L1 and TIM3 blockade improves expansion of fit human CD8(+) antigen-specific T cells for adoptive immunotherapy. Mol. Ther. Methods Clin. Dev. 2022, 27, 230–245. [Google Scholar] [CrossRef] [PubMed]
- Tian, T.; Li, Z. Targeting Tim-3 in Cancer With Resistance to PD-1/PD-L1 Blockade. Front. Oncol. 2021, 11, 731175. [Google Scholar] [CrossRef] [PubMed]
- Jiang, W.; Li, F.; Jiang, Y.; Li, S.; Liu, X.; Xu, Y.; Li, B.; Feng, X.; Zheng, C. Tim-3 Blockade Elicits Potent Anti-Multiple Myeloma Immunity of Natural Killer Cells. Front. Oncol. 2022, 12, 739976. [Google Scholar] [CrossRef]
- Laureano, R.S.; Sprooten, J.; Vanmeerbeerk, I.; Borras, D.M.; Govaerts, J.; Naulaerts, S.; Berneman, Z.N.; Beuselinck, B.; Bol, K.F.; Borst, J.; et al. Trial watch: Dendritic cell (DC)-based immunotherapy for cancer. Oncoimmunology 2022, 11, 2096363. [Google Scholar] [CrossRef]
- Ho, N.I.; Huis In ‘t Veld, L.G.M.; Raaijmakers, T.K.; Adema, G.J. Adjuvants Enhancing Cross-Presentation by Dendritic Cells: The Key to More Effective Vaccines? Front. Immunol. 2018, 9, 2874. [Google Scholar] [CrossRef]
- Perez, C.R.; De Palma, M. Engineering dendritic cell vaccines to improve cancer immunotherapy. Nat. Commun. 2019, 10, 5408. [Google Scholar] [CrossRef] [Green Version]
- Calmeiro, J.; Mendes, L.; Duarte, I.F.; Leitao, C.; Tavares, A.R.; Ferreira, D.A.; Gomes, C.; Serra, J.; Falcao, A.; Cruz, M.T.; et al. In-Depth Analysis of the Impact of Different Serum-Free Media on the Production of Clinical Grade Dendritic Cells for Cancer Immunotherapy. Front. Immunol. 2020, 11, 593363. [Google Scholar] [CrossRef]
- Marques, G.S.; Silva, Z.; Videira, P.A. Antitumor Efficacy of Human Monocyte-Derived Dendritic Cells: Comparing Effects of two Monocyte Isolation Methods. Biol. Proced. Online 2018, 20, 4. [Google Scholar] [CrossRef] [Green Version]
- Hatfield, P.; Merrick, A.E.; West, E.; O’Donnell, D.; Selby, P.; Vile, R.; Melcher, A.A. Optimization of dendritic cell loading with tumor cell lysates for cancer immunotherapy. J. Immunother. 2008, 31, 620–632. [Google Scholar] [CrossRef] [PubMed]
- Gu, Y.Z.; Zhao, X.; Song, X.R. Ex vivo pulsed dendritic cell vaccination against cancer. Acta Pharmacol. Sin. 2020, 41, 959–969. [Google Scholar] [CrossRef] [PubMed]
- Massa, C.; Thomas, C.; Wang, E.; Marincola, F.; Seliger, B. Different maturation cocktails provide dendritic cells with different chemoattractive properties. J. Transl. Med. 2015, 13, 175. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Castiello, L.; Sabatino, M.; Jin, P.; Clayberger, C.; Marincola, F.M.; Krensky, A.M.; Stroncek, D.F. Monocyte-derived DC maturation strategies and related pathways: A transcriptional view. Cancer Immunol. Immunother. CII 2011, 60, 457–466. [Google Scholar] [CrossRef] [Green Version]
- Dalod, M.; Chelbi, R.; Malissen, B.; Lawrence, T. Dendritic cell maturation: Functional specialization through signaling specificity and transcriptional programming. EMBO J. 2014, 33, 1104–1116. [Google Scholar] [CrossRef] [Green Version]
- Sandgren, S.; Wittrup, A.; Cheng, F.; Jonsson, M.; Eklund, E.; Busch, S.; Belting, M. The human antimicrobial peptide LL-37 transfers extracellular DNA plasmid to the nuclear compartment of mammalian cells via lipid rafts and proteoglycan-dependent endocytosis. J. Biol. Chem. 2004, 279, 17951–17956. [Google Scholar] [CrossRef] [Green Version]
- Badal, D.; Dayal, D.; Singh, G.; Sachdeva, N. Role of DNA-LL37 complexes in the activation of plasmacytoid dendritic cells and monocytes in subjects with type 1 diabetes. Sci. Rep. 2020, 10, 8896. [Google Scholar] [CrossRef]
- Carozza, J.A.; Bohnert, V.; Nguyen, K.C.; Skariah, G.; Shaw, K.E.; Brown, J.A.; Rafat, M.; von Eyben, R.; Graves, E.E.; Glenn, J.S.; et al. Extracellular cGAMP is a cancer cell-produced immunotransmitter involved in radiation-induced anti-cancer immunity. Nat. Cancer 2020, 1, 184–196. [Google Scholar] [CrossRef]
- Skopelja-Gardner, S.; An, J.; Tai, J.; Tanaka, L.; Sun, X.; Hermanson, P.; Baum, R.; Kawasumi, M.; Green, R.; Gale, M., Jr.; et al. The early local and systemic Type I interferon responses to ultraviolet B light exposure are cGAS dependent. Sci. Rep. 2020, 10, 7908. [Google Scholar] [CrossRef]
- Li, C.; Liu, W.; Wang, F.; Hayashi, T.; Mizuno, K.; Hattori, S.; Fujisaki, H.; Ikejima, T. DNA damage-triggered activation of cGAS-STING pathway induces apoptosis in human keratinocyte HaCaT cells. Mol. Immunol. 2021, 131, 180–190. [Google Scholar] [CrossRef]
- Wei, X.; Zhang, L.; Yang, Y.; Hou, Y.; Xu, Y.; Wang, Z.; Su, H.; Han, F.; Han, J.; Liu, P.; et al. LL-37 transports immunoreactive cGAMP to activate STING signaling and enhance interferon-mediated host antiviral immunity. Cell Rep. 2022, 39, 110880. [Google Scholar] [CrossRef] [PubMed]
- Yang, B.; Good, D.; Mosaiab, T.; Liu, W.; Ni, G.; Kaur, J.; Liu, X.; Jessop, C.; Yang, L.; Fadhil, R.; et al. Significance of LL-37 on Immunomodulation and Disease Outcome. BioMed Res. Int. 2020, 2020, 8349712. [Google Scholar] [CrossRef]
- Bals, R.; Wang, X.; Zasloff, M.; Wilson, J.M. The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface. Proc. Natl. Acad. Sci. USA 1998, 95, 9541–9546. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Oliveira-Bravo, M.; Sangiorgi, B.B.; Schiavinato, J.L.; Carvalho, J.L.; Covas, D.T.; Panepucci, R.A.; Neves, F.A.; Franco, O.L.; Pereira, R.W.; Saldanha-Araujo, F. LL-37 boosts immunosuppressive function of placenta-derived mesenchymal stromal cells. Stem Cell Res. Ther. 2016, 7, 189. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Alexandre-Ramos, D.S.; Silva-Carvalho, A.E.; Lacerda, M.G.; Serejo, T.R.T.; Franco, O.L.; Pereira, R.W.; Carvalho, J.L.; Neves, F.A.R.; Saldanha-Araujo, F. LL-37 treatment on human peripheral blood mononuclear cells modulates immune response and promotes regulatory T-cells generation. Biomed. Pharmacother. 2018, 108, 1584–1590. [Google Scholar] [CrossRef]
- Zhang, Z.; Chen, W.Q.; Zhang, S.Q.; Bai, J.X.; Lau, C.L.; Sze, S.C.; Yung, K.K.; Ko, J.K. The human cathelicidin peptide LL-37 inhibits pancreatic cancer growth by suppressing autophagy and reprogramming of the tumor immune microenvironment. Front. Pharmacol. 2022, 13, 906625. [Google Scholar] [CrossRef]
- Ito, T.; Smrž, D.; Jung, M.Y.; Bandara, G.; Desai, A.; Smržová, S.; Kuehn, H.S.; Beaven, M.A.; Metcalfe, D.D.; Gilfillan, A.M. Stem Cell Factor Programs the Mast Cell Activation Phenotype. J. Immunol. 2012, 188, 5428–5437. [Google Scholar] [CrossRef] [Green Version]
- Jung, M.Y.; Smrž, D.; Desai, A.; Bandara, G.; Ito, T.; Iwaki, S.; Kang, J.H.; Andrade, M.V.; Hilderbrand, S.C.; Brown, J.M.; et al. IL-33 Induces a Hyporesponsive Phenotype in Human and Mouse Mast Cells. J. Immunol. 2013, 190, 531–538. [Google Scholar] [CrossRef] [Green Version]
- Desai, A.; Jung, M.Y.; Olivera, A.; Gilfillan, A.M.; Prussin, C.; Kirshenbaum, A.S.; Beaven, M.A.; Metcalfe, D.D. IL-6 promotes an increase in human mast cell numbers and reactivity through suppression of suppressor of cytokine signaling 3. J. Allergy Clin. Immunol. 2016, 137, 1863–1871.e6. [Google Scholar] [CrossRef] [Green Version]
- Smrž, D.; Bandara, G.; Beaven, M.A.; Metcalfe, D.D.; Gilfillan, A.M. Prevention of F-actin assembly switches the response to SCF from chemotaxis to degranulation in human mast cells. Eur. J. Immunol. 2013, 43, 1873–1882. [Google Scholar] [CrossRef] [Green Version]
- Zheng, Y.; Niyonsaba, F.; Ushio, H.; Nagaoka, I.; Ikeda, S.; Okumura, K.; Ogawa, H. Cathelicidin LL-37 induces the generation of reactive oxygen species and release of human alpha-defensins from neutrophils. Br. J. Dermatol. 2007, 157, 1124–1131. [Google Scholar] [CrossRef] [PubMed]
- Lande, R.; Gregorio, J.; Facchinetti, V.; Chatterjee, B.; Wang, Y.H.; Homey, B.; Cao, W.; Wang, Y.H.; Su, B.; Nestle, F.O.; et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 2007, 449, 564–569. [Google Scholar] [CrossRef] [PubMed]
- Ganguly, D.; Chamilos, G.; Lande, R.; Gregorio, J.; Meller, S.; Facchinetti, V.; Homey, B.; Barrat, F.J.; Zal, T.; Gilliet, M. Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J. Exp. Med. 2009, 206, 1983–1994. [Google Scholar] [CrossRef] [PubMed]
- Niyonsaba, F.; Ushio, H.; Nakano, N.; Ng, W.; Sayama, K.; Hashimoto, K.; Nagaoka, I.; Okumura, K.; Ogawa, H. Antimicrobial peptides human beta-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokines. J. Investig. Dermatol. 2007, 127, 594–604. [Google Scholar] [CrossRef] [Green Version]
- Cheng, M.; Ho, S.; Yoo, J.H.; Tran, D.H.; Bakirtzi, K.; Su, B.; Tran, D.H.; Kubota, Y.; Ichikawa, R.; Koon, H.W. Cathelicidin suppresses colon cancer development by inhibition of cancer associated fibroblasts. Clin. Exp. Gastroenterol. 2015, 8, 13–29. [Google Scholar] [CrossRef] [Green Version]
- Pinheiro da Silva, F.; Gallo, R.L.; Nizet, V. Differing effects of exogenous or endogenous cathelicidin on macrophage toll-like receptor signaling. Immunol. Cell Biol. 2009, 87, 496–500. [Google Scholar] [CrossRef] [Green Version]
- Hu, Z.; Murakami, T.; Suzuki, K.; Tamura, H.; Reich, J.; Kuwahara-Arai, K.; Iba, T.; Nagaoka, I. Antimicrobial cathelicidin peptide LL-37 inhibits the pyroptosis of macrophages and improves the survival of polybacterial septic mice. Int. Immunol. 2016, 28, 245–253. [Google Scholar] [CrossRef] [Green Version]
- Torres-Juarez, F.; Cardenas-Vargas, A.; Montoya-Rosales, A.; Gonzalez-Curiel, I.; Garcia-Hernandez, M.H.; Enciso-Moreno, J.A.; Hancock, R.E.; Rivas-Santiago, B. LL-37 immunomodulatory activity during Mycobacterium tuberculosis infection in macrophages. Infect. Immun. 2015, 83, 4495–4503. [Google Scholar] [CrossRef] [Green Version]
- Chuang, C.M.; Monie, A.; Wu, A.; Mao, C.P.; Hung, C.F. Treatment with LL-37 peptide enhances antitumor effects induced by CpG oligodeoxynucleotides against ovarian cancer. Hum. Gene Ther. 2009, 20, 303–313. [Google Scholar] [CrossRef] [Green Version]
- Ji, P.; Zhou, Y.; Yang, Y.; Wu, J.; Zhou, H.; Quan, W.; Sun, J.; Yao, Y.; Shang, A.; Gu, C.; et al. Myeloid cell-derived LL-37 promotes lung cancer growth by activating Wnt/beta-catenin signaling. Theranostics 2019, 9, 2209–2223. [Google Scholar] [CrossRef]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 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
Stakheev, D.; Taborska, P.; Kalkusova, K.; Bartunkova, J.; Smrz, D. LL-37 as a Powerful Molecular Tool for Boosting the Performance of Ex Vivo-Produced Human Dendritic Cells for Cancer Immunotherapy. Pharmaceutics 2022, 14, 2747. https://doi.org/10.3390/pharmaceutics14122747
Stakheev D, Taborska P, Kalkusova K, Bartunkova J, Smrz D. LL-37 as a Powerful Molecular Tool for Boosting the Performance of Ex Vivo-Produced Human Dendritic Cells for Cancer Immunotherapy. Pharmaceutics. 2022; 14(12):2747. https://doi.org/10.3390/pharmaceutics14122747
Chicago/Turabian StyleStakheev, Dmitry, Pavla Taborska, Katerina Kalkusova, Jirina Bartunkova, and Daniel Smrz. 2022. "LL-37 as a Powerful Molecular Tool for Boosting the Performance of Ex Vivo-Produced Human Dendritic Cells for Cancer Immunotherapy" Pharmaceutics 14, no. 12: 2747. https://doi.org/10.3390/pharmaceutics14122747
APA StyleStakheev, D., Taborska, P., Kalkusova, K., Bartunkova, J., & Smrz, D. (2022). LL-37 as a Powerful Molecular Tool for Boosting the Performance of Ex Vivo-Produced Human Dendritic Cells for Cancer Immunotherapy. Pharmaceutics, 14(12), 2747. https://doi.org/10.3390/pharmaceutics14122747