Vacunación profiláctica con células dendríticas sobre la respuesta inmune antitumoral y el crecimiento tumoral en un modelo de ratón de cáncer de mama

Autores/as

DOI:

https://doi.org/10.33448/rsd-v10i13.20905

Palabras clave:

Cáncer; Células Dendríticas; Vacunación ; Immunoterapia; Inmunidad tumoral.

Resumen

Las vacunas de células dendríticas han mostrado resultados prometedores para tumores poco inmunogénicos y pueden promover la generación de mejores respuestas inmunitarias en el microambiente tumoral. Por lo tanto, este estudio evalúa la influencia de la vacunación profiláctica con células dendríticas sobre la respuesta inmune antitumoral en el microambiente tumoral y sobre el crecimiento tumoral, en un modelo experimental de cáncer de mama inducido por 4T1. Por tanto, los ratones Balb / c se separaron en un grupo vacunado y un grupo no vacunado. La vacuna de células dendríticas se diferenciaba y maduraba ex vivo a partir de la médula ósea. Durante el período experimental, se controlaron periódicamente los volúmenes tumorales. Los tumores fueron evaluados para células inmunes (linfocitos T colaboradores y linfocitos T citotóxicos), perfil T colaborador (Th1, Th2, Th17 y Treg), síntesis de TNF-α e IFN-γ por linfocitos T citotóxicos y Th1. El grupo previamente vacunado tenía un volumen tumoral reducido (14.0, 0-131.7) en comparación con el grupo no vacunado (89.59, 0.1250-459,6) (p = 0.0421). Los subtipos Th1, Th2, Th17, Treg, T citotóxicos, incluidos TNF-α e IFN-γ producidos por Th1 y T citotóxico, mostraron un aumento significativo en el grupo vacunado, al igual que el equilibrio de Th1 / Th2 y Th1 / Treg. Los resultados mostraron que la vacunación profiláctica con células dendríticas mostró un efecto antitumoral considerable en el modelo estudiado, promoviendo un aumento en la activación de células importantes en la respuesta inmune y una reducción del volumen tumoral. Los datos proporcionan evidencia de una activación oportuna de la vigilancia inmunológica en ausencia de carga tumoral.

Citas

Ahrends, T., Busselaar, J., Severson, T. M., Bąbała, N., de Vries, E., Bovens, A., Wessels, L., van Leeuwen, F., & Borst, J. (2019). CD4+ T cell help creates memory CD8+ T cells with innate and help-independent recall capacities. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-13438-1

Aly, H. A. A. (2012). Cancer therapy and vaccination. Journal of Immunological Methods, 382(1–2), 1–23. https://doi.org/10.1016/j.jim.2012.05.014

Anguille, S., Smits, E. L., Lion, E., van Tendeloo, V. F., & Berneman, Z. N. (2014). Clinical use of dendritic cells for cancer therapy. The Lancet Oncology, 15(7), e257–e267. https://doi.org/10.1016/S1470-2045(13)70585-0

Balkwill, F. (2011). The Inflammatory Tissue Microenvironment and the Early Stages of Malignancy. In Pre-Invasive Disease: Pathogenesis and Clinical Management (pp. 21–29). Springer New York. https://doi.org/10.1007/978-1-4419-6694-0_2

Balkwill, F. R. (2012). The chemokine system and cancer. The Journal of Pathology, 226(2), 148–157. https://doi.org/10.1002/path.3029

Banchereau, J., & Steinman, R. M. (1998). Dendritic cells and the control of immunity. Nature, 392(6673), 245–252. https://doi.org/10.1038/32588

Bauer, C., Dauer, M., Saraj, S., Schnurr, M., Bauernfeind, F., Sterzik, A., Junkmann, J., Jakl, V., Kiefl, R., Oduncu, F., Emmerich, B., Mayr, D., Mussack, T.,

Bruns, C., Rüttinger, D., Conrad, C., Jauch, K.-W., Endres, S., & Eigler, A. (2011). Dendritic cell-based vaccination of patients with advanced pancreatic carcinoma: results of a pilot study. Cancer Immunology, Immunotherapy, 60(8), 1097–1107. https://doi.org/10.1007/s00262-011-1023-5

Burke, J. D., & Young, H. A. (2019). IFN-Γ: A cytokine at the right time, is in the right place. In Seminars in Immunology (Vol. 43). Academic Press. https://doi.org/10.1016/j.smim.2019.05.002

Burnet, F. M. (1970). The concept of immunological surveillance. In Progress in experimental tumor research. Fortschritte der experimentellen Tumorforschung. Progres de la recherche experimentale des tumeurs. https://doi.org/10.1159/000386035

Chemin, K., Gerstner, C., & Malmström, V. (2019). Effector Functions of CD4+ T Cells at the Site of Local Autoimmune Inflammation—Lessons From Rheumatoid Arthritis. Frontiers in Immunology, 10. https://doi.org/10.3389/fimmu.2019.00353

Corthay, A., Skovseth, D. K., Lundin, K. U., Røsjø, E., Omholt, H., Hofgaard, P. O., Haraldsen, G., & Bogen, B. (2005). Primary Antitumor Immune Response Mediated by CD4+ T Cells. Immunity, 22(3), 371–383. https://doi.org/10.1016/j.immuni.2005.02.003

Cunha, L. L., Morari, E. C., Nonogaki, S., Bufalo, N. E., da Assumpção, L. V. M., Soares, F. A., Vassallo, J., & Ward, L. S. (2020). RORγt may Influence the Microenvironment of Thyroid Cancer Predicting Favorable Prognosis. Scientific Reports, 10(1), 4142. https://doi.org/10.1038/s41598-020-60280-3

da Cunha, A., Antoniazi Michelin, M., & Cândido Murta, E. F. (2016). Phenotypic profile of dendritic and T cells in the lymph node of Balb/C mice with breast cancer submitted to dendritic cells immunotherapy. Immunology Letters. https://doi.org/10.1016/j.imlet.2016.07.009

Drake, C. G. (2011). Update on Prostate Cancer Vaccines. The Cancer Journal, 17(5), 294–299. https://doi.org/10.1097/PPO.0b013e3182325e78

Durgeau, A., Virk, Y., Corgnac, S., & Mami-Chouaib, F. (2018). Recent advances in targeting CD8 T-cell immunity for more effective cancer immunotherapy. In Frontiers in Immunology (Vol. 9, Issue JAN). Frontiers Media S.A. https://doi.org/10.3389/fimmu.2018.00014

Egberts, J. H., Cloosters, V., Noack, A., Schniewind, B., Thon, L., Klose, S., Kettler, B., Von Forstner, C., Kneitz, C., Tepel, J., Adam, D., Wajant, H., Kalthoff, H., & Trauzold, A. (2008). Anti-tumor necrosis factor therapy inhibits pancreatic tumor growth and metastasis. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-07-5704

Farhood, B., Najafi, M., & Mortezaee, K. (2019). CD8+ cytotoxic T lymphocytes in cancer immunotherapy: A review. In Journal of Cellular Physiology (Vol. 234, Issue 6, pp. 8509–8521). Wiley-Liss Inc. https://doi.org/10.1002/jcp.27782

Fong, L., Brockstedt, D., Benike, C., Wu, L., & Engleman, E. G. (2001). Dendritic Cells Injected Via Different Routes Induce Immunity in Cancer Patients. The Journal of Immunology, 166(6), 4254–4259. https://doi.org/10.4049/jimmunol.166.6.4254

Fu, C., & Jiang, A. (2018). Dendritic Cells and CD8 T Cell Immunity in Tumor Microenvironment. In Frontiers in immunology (Vol. 9, p. 3059). NLM (Medline). https://doi.org/10.3389/fimmu.2018.03059

Hong, X., Dong, T., Hu, J., Yi, T., Li, W., Zhang, Z., Lin, S., & Niu, W. (2013). Synergistical toll-like receptors activated dendritic cells induce antitumor effects against carcinoembryonic antigen-expressing colon cancer. International Journal of Colorectal Disease, 28(1), 25–33. https://doi.org/10.1007/s00384-012-1530-7

Jorgovanovic, D., Song, M., Wang, L., & Zhang, Y. (2020). Roles of IFN-γin tumor progression and regression: A review. In Biomarker Research (Vol. 8, Issue 1). BioMed Central Ltd. https://doi.org/10.1186/s40364-020-00228-x

Kachler, K., Holzinger, C., Trufa, D. I., Sirbu, H., & Finotto, S. (2018). The role of Foxp3 and Tbet co-expressing Treg cells in lung carcinoma. OncoImmunology. https://doi.org/10.1080/2162402X.2018.1456612

Kandalaft, L. E., Powell, Jr., D. J., Chiang, C. L., Tanyi, J., Kim, S., Bosch, M., Montone, K., Mick, R., Levine, B. L., Torigian, D. A., June, C. H., & Coukos, G. (2013). Autologous lysate-pulsed dendritic cell vaccination followed by adoptive transfer of vaccine-primed ex vivo co-stimulated T cells in recurrent ovarian cancer. OncoImmunology, 2(1), e22664. https://doi.org/10.4161/onci.22664

Kantoff, P. W., Higano, C. S., Shore, N. D., Berger, E. R., Small, E. J., Penson, D. F., Redfern, C. H., Ferrari, A. C., Dreicer, R., Sims, R. B., Xu, Y., Frohlich, M. W., & Schellhammer, P. F. (2010). Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer. New England Journal of Medicine, 363(5), 411–422. https://doi.org/10.1056/NEJMoa1001294

Koido, S., Kashiwaba, M., Chen, D., Gendler, S., Kufe, D., & Gong, J. (2000). Induction of Antitumor Immunity by Vaccination of Dendritic Cells Transfected with MUC1 RNA. The Journal of Immunology, 165(10), 5713–5719. https://doi.org/10.4049/jimmunol.165.10.5713

Korkaya, H., Liu, S., & Wicha, M. S. (2011). Breast cancer stem cells, cytokine networks, and the tumor microenvironment. The Journal of Clinical Investigation, 121(10), 3804–3809. https://doi.org/10.1172/JCI57099

Lanzavecchia, A., & Sallusto, F. (2005). Understanding the generation and function of memory T cell subsets. In Current Opinion in Immunology. https://doi.org/10.1016/j.coi.2005.04.010

Lee, H. L., Jang, J. W., Lee, S. W., Yoo, S. H., Kwon, J. H., Nam, S. W., Bae, S. H., Choi, J. Y., Han, N. I., & Yoon, S. K. (2019). Inflammatory cytokines and change of Th1/Th2 balance as prognostic indicators for hepatocellular carcinoma in patients treated with transarterial chemoembolization. Scientific Reports, 9(1), 3260. https://doi.org/10.1038/s41598-019-40078-8

Lin, J. H., Huffman, A. P., Wattenberg, M. M., Walter, D. M., Carpenter, E. L., Feldser, D. M., Beatty, G. L., Furth, E. E., & Vonderheide, R. H. (2020). Type 1 conventional dendritic cells are systemically dysregulated early in pancreatic carcinogenesis. Journal of Experimental Medicine, 217(8). https://doi.org/10.1084/jem.20190673

Liudahl, S. M., & Coussens, L. M. (2017). To Help or To Harm: Dynamic Roles of CD4+ T Helper Cells in Solid Tumor Microenvironments. In Immunology: Immunotoxicology, Immunopathology, and Immunotherapy. https://doi.org/10.1016/B978-0-12-809819-6.00008-3

Lokhov, P. G., & Balashova, E. E. (2010). Cellular Cancer Vaccines: an Update on the Development of Vaccines Generated from Cell Surface Antigens. Journal of Cancer, 230–241. https://doi.org/10.7150/jca.1.230

Lopes, A. M. M., Michelin, M. A., & Murta, E. F. C. (2017). Monocyte-derived dendritic cells from patients with cervical intraepithelial lesions. Oncology Letters. https://doi.org/10.3892/ol.2017.5595

Lurje, I., Hammerich, L., & Tacke, F. (2020). Dendritic cell and T cell crosstalk in liver fibrogenesis and hepatocarcinogenesis: Implications for prevention and therapy of liver cancer. In International Journal of Molecular Sciences (Vol. 21, Issue 19, pp. 1–25). MDPI AG. https://doi.org/10.3390/ijms21197378

Maccalli, C., Parmiani, G., & Ferrone, S. (2017). Immunomodulating and Immunoresistance Properties of Cancer-Initiating Cells: Implications for the Clinical Success of Immunotherapy. Immunological Investigations, 46(3), 221–238. https://doi.org/10.1080/08820139.2017.1280051

Mahmoud, S., Lee, A., Ellis, I., & Green, A. R. (2012). Cd8+ T lymphocytes infiltrating breast cancer a promising new prognostic marker? OncoImmunology. https://doi.org/10.4161/onci.18614

Mahmoud, S. M. A., Paish, E. C., Powe, D. G., Macmillan, R. D., Grainge, M. J., Lee, A. H. S., Ellis, I. O., & Green, A. R. (2011). Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. Journal of Clinical Oncology. https://doi.org/10.1200/JCO.2010.30.5037

Markov, O. V., Mironova, N. L., Sennikov, S. V., Vlassov, V. V., & Zenkova, M. A. (2015). Prophylactic Dendritic Cell-Based Vaccines Efficiently Inhibit Metastases in Murine Metastatic Melanoma. PLOS ONE, 10(9), e0136911. https://doi.org/10.1371/journal.pone.0136911

Martínez-Lostao, L., Anel, A., & Pardo, J. (2015). How Do Cytotoxic Lymphocytes Kill Cancer Cells? Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-15-0685

Matheoud, D., Perié, L., Hoeffel, G., Vimeux, L., Parent, I., Marañón, C., Bourdoncle, P., Renia, L., Prevost-Blondel, A., Lucas, B., Feuillet, V., & Hosmalin, A. (2010). Cross-presentation by dendritic cells from live cells induces protective immune responses in vivo. Blood, 115(22), 4412–4420. https://doi.org/10.1182/blood-2009-11-255935

Mathis, D., & Benoist, C. (2004). Back to Central Tolerance. Immunity, 20(5), 509–516. https://doi.org/10.1016/S1074-7613(04)00111-6

Matias, B. F., De Oliveira, T. M., Rodrigues, C. M., Abdalla, D. R., Montes, L., Murta, E. F. C., & Michelin, M. A. (2013). Influence of Immunotherapy with Autologous Dendritic Cells on Innate and Adaptive Immune Response in Cancer. Clinical Medicine Insights: Oncology, 7, CMO.S12268. https://doi.org/10.4137/CMO.S12268

Mercogliano, M. F., Bruni, S., Elizalde, P. V., & Schillaci, R. (2020). Tumor Necrosis Factor α Blockade: An Opportunity to Tackle Breast Cancer. In Frontiers in Oncology. https://doi.org/10.3389/fonc.2020.00584

O’Neill, L. A. J., & Pearce, E. J. (2016). Immunometabolism governs dendritic cell and macrophage function. Journal of Experimental Medicine, 213(1), 15–23. https://doi.org/10.1084/jem.20151570

Ott, E., Bilonda, L., Dansette, D., Deleine, C., Duchalais, E., Podevin, J., Volteau, C., Bennouna, J., Touchefeu, Y., Fourquier, P., El Alami Thomas, W., Chetritt, J., Bezieau, S., Denis, M., Toquet, C., Mosnier, J. F., Jarry, A., & Bossard, C. (2019). The density of Tbet+ tumor-infiltrating T lymphocytes reflects an effective and druggable preexisting adaptive antitumor immune response in colorectal cancer, irrespective of the microsatellite status. OncoImmunology. https://doi.org/10.1080/2162402X.2018.1562834

Palucka, K., & Banchereau, J. (2012). Cancer immunotherapy via dendritic cells. Nature Reviews Cancer, 12(4), 265–277. https://doi.org/10.1038/nrc3258

Palucka, K., & Banchereau, J. (2013). Dendritic-Cell-Based Therapeutic Cancer Vaccines. Immunity, 39(1), 38–48. https://doi.org/10.1016/j.immuni.2013.07.004

Pardoll, D. M., & Topalian, S. L. (1998). The role of CD4+ T cell responses in antitumor immunity. Current Opinion in Immunology, 10(5), 588–594. https://doi.org/10.1016/S0952-7915(98)80228-8

Perez, C. R., & De Palma, M. (2019). Engineering dendritic cell vaccines to improve cancer immunotherapy. In Nature Communications. https://doi.org/10.1038/s41467-019-13368-y

Phuphanich, S., Wheeler, C. J., Rudnick, J. D., Mazer, M., Wang, H., Nuño, M. A., Richardson, J. E., Fan, X., Ji, J., Chu, R. M., Bender, J. G., Hawkins, E. S., Patil, C. G., Black, K. L., & Yu, J. S. (2013). Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma. Cancer Immunology, Immunotherapy, 62(1), 125–135. https://doi.org/10.1007/s00262-012-1319-0

Rodrigues, C. M., Matias, B. F., Murta, E. F. C., & Michelin, M. A. (2011). The Role of T Lymphocytes in Cancer Patients Undergoing Immunotherapy with Autologous Dendritic Cells. Clinical Medicine Insights: Oncology, 5, CMO.S6927. https://doi.org/10.4137/CMO.S6927

Roland, C. L., Dineen, S. P., Lynn, K. D., Sullivan, L. A., Dellinger, M. T., Sadegh, L., Sullivan, J. P., Shames, D. S., & Brekken, R. A. (2009). Inhibition of vascular endothelial growth factor reduces angiogenesis and modulates immune cell infiltration of orthotopic breast cancer xenografts. Molecular Cancer Therapeutics, 8(7), 1761–1771. https://doi.org/10.1158/1535-7163.MCT-09-0280

Sabado, R. L., Balan, S., & Bhardwaj, N. (2017). Dendritic cell-based immunotherapy. In Cell Research. https://doi.org/10.1038/cr.2016.157

Sallusto, F., Geginat, J., & Lanzavecchia, A. (2004). C entral M emory and E ffector M emory T C ell S ubsets : Function, Generation, and Maintenance . Annual Review of Immunology. https://doi.org/10.1146/annurev.immunol.22.012703.104702

Sallusto, F., & Lanzavecchi, A. (1994). Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus iuterleukin 4 and downregulated by tumor necrosis factor α. Journal of Experimental Medicine. https://doi.org/10.1084/jem.179.4.1109

Seledtsov, V., Goncharov, A., & Seledtsova, G. (2015). Clinically feasible approaches to potentiating cancer cell-based immunotherapies. Human Vaccines & Immunotherapeutics, 11(4), 851–869. https://doi.org/10.1080/21645515.2015.1009814

Shangguan, A., Shang, N., Figini, M., Pan, L., Yang, J., Ma, Q., Hu, S., Eresen, A., Sun, C., Wang, B., Velichko, Y., Yaghmai, V., & Zhang, Z. (2020). Prophylactic dendritic cell vaccination controls pancreatic cancer growth in a mouse model. Cytotherapy, 22(1), 6–15. https://doi.org/10.1016/j.jcyt.2019.12.001

Simon, T., Fonteneau, J.-F., & Grégoire, M. (2009). Dendritic cell preparation for immunotherapeutic interventions. Immunotherapy, 1(2), 289–302. https://doi.org/10.2217/1750743X.1.2.289

Stanton, S. E., & Disis, M. L. (2016). Clinical significance of tumor-infiltrating lymphocytes in breast cancer. https://doi.org/10.1186/s40425-016-0165-6

Tindemans, I., Serafini, N., DiSanto, J. P., & Hendriks, R. W. (2014). GATA-3 function in innate and adaptive immunity. In Immunity. https://doi.org/10.1016/j.immuni.2014.06.006

Töpfer, K., Kempe, S., Müller, N., Schmitz, M., Bachmann, M., Cartellieri, M., Schackert, G., & Temme, A. (2011). Tumor Evasion from T Cell Surveillance. Journal of Biomedicine and Biotechnology, 2011, 1–19. https://doi.org/10.1155/2011/918471

Tosolini, M., Kirilovsky, A., Mlecnik, B., Fredriksen, T., Mauger, S., Bindea, G., Berger, A., Bruneval, P., Fridman, W. H., Pagès, F., & Galon, J. (2011). Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, Th2, Treg, Th17) in patients with colorectal cancer. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-10-2907

Vik-Mo, E. O., Nyakas, M., Mikkelsen, B. V., Moe, M. C., Due-Tønnesen, P., Suso, E. M. I., Sæbøe-Larssen, S., Sandberg, C., Brinchmann, J. E., Helseth, E., Rasmussen, A.-M., Lote, K., Aamdal, S., Gaudernack, G., Kvalheim, G., & Langmoen, I. A. (2013). Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma. Cancer Immunology, Immunotherapy, 62(9), 1499–1509. https://doi.org/10.1007/s00262-013-1453-3

Wculek, S. K., Cueto, F. J., Mujal, A. M., Melero, I., Krummel, M. F., & Sancho, D. (2020). Dendritic cells in cancer immunology and immunotherapy. In Nature Reviews Immunology (Vol. 20, Issue 1, pp. 7–24). Nature Research. https://doi.org/10.1038/s41577-019-0210-z

Zong, J., Keskinov, A. A., Shurin, G. V., & Shurin, M. R. (2016). Tumor-derived factors modulating dendritic cell function. Cancer Immunology, Immunotherapy, 65(7), 821–833. https://doi.org/10.1007/s00262-016-1820-y

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05/10/2021

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VIEIRA, J. F.; MURTA, E. F. C. .; MICHELIN, M. A. . Vacunación profiláctica con células dendríticas sobre la respuesta inmune antitumoral y el crecimiento tumoral en un modelo de ratón de cáncer de mama . Research, Society and Development, [S. l.], v. 10, n. 13, p. e100101320905, 2021. DOI: 10.33448/rsd-v10i13.20905. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/20905. Acesso em: 17 jul. 2024.

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