EVASÃO DA RESPOSTA IMUNE NO CÂNCER DE PRÓSTATA: PAPEL DO MICROAMBIENTE TUMORAL
DOI:
https://doi.org/10.56238/10.56238/levv16n54-050Palavras-chave:
Neoplasia, Mediadores Imunes, Mecanismo Imunes, ImunoterapiaResumo
Introdução: O câncer de próstata (CaP) é uma das neoplasias mais prevalentes entre os homens, com alta taxa de incidência e mortalidade. Em 2022, foram registrados 1.467.854 casos e 397.430 óbitos globalmente. No Brasil, o CaP é o mais diagnosticado entre homens, com 71.730 novos casos em 2023. A doença é caracterizada pela proliferação descontrolada de células tumorais e pela evasão da resposta imunológica, facilitando a metástase. Objetivo: Diante deste cenário, o presente trabalho teve como objetivo desvendar o processo de crescimento do câncer, com ênfase no papel do microambiente tumoral e sua atuação na evasão da resposta imunológica. Metodologia: Este estudo foi realizado por meio de uma revisão da literatura, utilizando fontes acadêmicas contemporâneas. A pesquisa focou na análise descritiva das interações entre o microambiente tumoral (MAT) e a resposta imune no contexto do câncer de próstata, abrangendo publicações de 2015 a 2025. Resultados: O microambiente tumoral desempenha um papel crucial na progressão do CaP, criando condições imunossupressoras que favorecem a sobrevivência das células tumorais. As células do MAT secretam fatores que inibem a resposta do sistema imunológico, dificultando a eliminação das células cancerígenas. Conclusão: A complexidade do MAT representa um desafio significativo para a eficácia das terapias disponíveis para o CaP. A detecção precoce da doença é fundamental para melhorar o prognóstico dos pacientes. A continuidade da pesquisa em novas terapias é essencial para o desenvolvimento de estratégias que possam superar as barreiras impostas pelo microambiente tumoral.
Downloads
Referências
ARCE-SILLAS, Asiel et al. Regulatory T cells: molecular actions on effector cells in immune regulation. Journal of immunology research, v. 2016, n. 1, p. 1720827, 2016. DOI: https://doi.org/10.1155/2016/1720827
ARNETH, Borros. Tumor microenvironment. Medicina, v. 56, n. 1, p. 15, 2019. DOI: https://doi.org/10.3390/medicina56010015
BOŻYK, Aleksandra et al. Tumor microenvironment—A short review of cellular and interaction diversity. Biology, v. 11, n. 6, p. 929, 2022. DOI: https://doi.org/10.3390/biology11060929
BIED, Mathilde et al. Roles of macrophages in tumor development: a spatiotemporal perspective. Cellular & molecular immunology, v. 20, n. 9, p. 983-992, 2023. DOI: https://doi.org/10.1038/s41423-023-01061-6
DE ALMEIDA, Daniel Vargas P. et al. Immune checkpoint blockade for prostate cancer: niche role or next breakthrough? In: American Society of Clinical Oncology Educational book. American Society of Clinical Oncology. Annual Meeting. 2020. p. 1-18. DOI: https://doi.org/10.1200/EDBK_278853
DEEP, Gagan; PANIGRAHI, Gati K. Hypoxia-induced signaling promotes prostate cancer progression: exosomes role as messenger of hypoxic response in tumor microenvironment. Critical Reviews™ in Oncogenesis, v. 20, n. 5-6, 2015. DOI: https://doi.org/10.1615/CritRevOncog.v20.i5-6.130
DIKIY, S. Principles of regulatory T cell function. Trends in Immunology, 2023. Disponível em: https://www.cell.com/trends/immunology/fulltext/S1471-4906(23)00019-2. Acesso em: 24 out. 2025. DOI: 10.1016/j.it.2023.01.003. DOI: https://doi.org/10.1016/j.it.2023.01.003
FENG, Dechao et al. Cellular landscape of tumour microenvironment in prostate cancer. Immunology, v. 168, n. 2, p. 199-202, 2023. DOI: https://doi.org/10.1111/imm.13456
GIACOMINI, Arianna et al. The FGF/FGFR system in the physiopathology of the prostate gland. Physiological reviews, v. 101, n. 2, p. 569-610, 2021. DOI: https://doi.org/10.1152/physrev.00005.2020
GLOBOCAN, Goblal Cancer Observatory. Prostate cancer today, 2024. Disponível em: https://gco.iarc.who.int/media/globocan/factsheets/cancers/27-prostate-fact-sheet.pdf. Acesso em: 1 de maio de 2025.
GOSWAMI, T. K. et al. Regulatory T cells (Tregs) and their therapeutic potential. Frontiers in Immunology, v. 13, p. 9009914, 2022. DOI: 10.3389/fimmu.2022.9009914.
GROVER, P. et al. Regulatory T cells: Regulation of identity and function. Frontiers in Immunology, v. 12, p. 750542, 2021. DOI: 10.3389/fimmu.2021.750542. DOI: https://doi.org/10.3389/fimmu.2021.750542
HALL, John E. (Ed.). Guyton & Hall. Tratado de fisiología médica. Elsevier Health Sciences, 2021.
HAN, Chenglin et al. The roles of tumor‐associated macrophages in prostate cancer. Journal of oncology, v. 2022, n. 1, p. 8580043, 2022. DOI: https://doi.org/10.1155/2022/8580043
HANAHAN, Douglas. Hallmarks of cancer: new dimensions. Cancer discovery, v. 12, n. 1, p. 31-46, 2022. DOI: https://doi.org/10.1158/2159-8290.CD-21-1059
HUANG, T. et al. Tumor-infiltrating regulatory T cell: A promising therapeutic target. OncoImmunology, v. 13, n. 1, p. 11706582, 2024. DOI: 10.1080/2162402X.2024.11706582.
HUANG, Xueqin et al. Neutrophils in Cancer immunotherapy: friends or foes?. Molecular cancer, v. 23, n. 1, p. 107, 2024. DOI: https://doi.org/10.1186/s12943-024-02004-z
HAWLINA, Simon; CHOWDHURY, Helena H.; SMRKOLJ, Tomaž; ZOREC, Robert. Dendritic cell-based vaccine prolongs survival and time to next therapy independently of the vaccine cell number. Biology Direct, v. 17, n. 1, p. 5, 23 fev. 2022. DOI: https://doi.org/10.1186/s13062-022-00318-w
HAWLINA, S.; et al. Potential of Personalized Dendritic Cell-Based Immunohybridoma Vaccines to Treat Prostate Cancer. Life, v. 13, n. 7, p. 1498, 2023. DOI: https://doi.org/10.3390/life13071498
HERRERA, Mercedes et al. A snapshot of the tumor microenvironment in colorectal cancer: the liquid biopsy. International journal of molecular sciences, v. 20, n. 23, p. 6016, 2019. DOI: https://doi.org/10.3390/ijms20236016
HIFU prostate, 2025. Disponivel em: https://www.hifu-prostata.com.br/cancer-de-prostata/diagnostico-e-classificacao/ Acesso em: 12 de agosto de 2025.
INCA, Institutos Nacional do Câncer. Estatísticas sobre Câncer, 2025. Disponível em: https://www.gov.br/inca/pt-br/assuntos/cancer/numeros. Acesso em: 1 de maio de 2025.
JIMENEZ-MORALES, Silvia et al. Mechanisms of immunosuppressive tumor evasion: focus on acute lymphoblastic leukemia. Frontiers in immunology, v. 12, p. 737340, 2021. DOI: https://doi.org/10.3389/fimmu.2021.737340
KATOPODI, Theodora et al. Tumor-infiltrating dendritic cells: decisive roles in cancer immunosurveillance, immunoediting, and tumor T cell tolerance. Cells, v. 11, n. 20, p. 3183, 2022. DOI: https://doi.org/10.3390/cells11203183
KOINIS, Filippos et al. Myeloid-derived suppressor cells in prostate cancer: present knowledge and future perspectives. Cells, v. 11, n. 1, p. 20, 2021. DOI: https://doi.org/10.3390/cells11010020
KUMAR, Vinay; ABBAS, Abul K.; ASTER, Jon C. Robbins y Cotran. Patología estructural y funcional. Elsevier Health Sciences, 2021.
LESLIE SW, Soon-Sutton TL, Skelton WP. Prostate Cancer. 2024 Oct 4. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025.
LI, Kai et al. Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer. Signal transduction and targeted therapy, v. 6, n. 1, p. 362, 2021. DOI: https://doi.org/10.1038/s41392-021-00670-9
LIU, et al. Reversing the “cold” tumor microenvironment: the role of neoantigen vaccines in prostate cancer. [S.l.]: [s.n.], 2025.
LIU, Tongyan et al. Cancer-associated fibroblasts: an emerging target of anti-cancer immunotherapy. Journal of hematology & oncology, v. 12, n. 1, p. 86, 2019. DOI: https://doi.org/10.1186/s13045-019-0770-1
MELO, Camila Morais et al. The role of somatic mutations on the immune response of the tumor microenvironment in prostate cancer. International Journal of Molecular Sciences, v. 22, n. 17, p. 9550, 2021. DOI: https://doi.org/10.3390/ijms22179550
MOLINA, O. E. et al. Regulatory and memory T lymphocytes infiltrating prostate cancer tissue. Frontiers in Immunology, v. 15, p. 11180786, 2024. DOI: https://doi.org/10.3389/fimmu.2024.1372837
MOHAMED, Osama AA et al. The role of hypoxia on prostate cancer progression and metastasis. Molecular biology reports, v. 50, n. 4, p. 3873-3884, 2023. DOI: https://doi.org/10.1007/s11033-023-08251-5
NIU, Fanglin et al. Arginase: An emerging and promising therapeutic target for cancer treatment. Biomedicine & Pharmacotherapy, v. 149, p. 112840, 2022. DOI: https://doi.org/10.1016/j.biopha.2022.112840
NORDBY, Yngve et al. High expression of PDGFR-β in prostate cancer stroma is independently associated with clinical and biochemical prostate cancer recurrence. Scientific reports, v. 7, n. 1, p. 43378, 2017. DOI: https://doi.org/10.1038/srep43378
NOVYSEDLAK, Rene et al. The immune microenvironment in prostate cancer: a comprehensive review. Oncology, v. 103, n. 6, p. 521-545, 2025. DOI: https://doi.org/10.1159/000541881
PAN, Yueyun et al. Tumor-associated macrophages in tumor immunity. Frontiers in immunology, v. 11, p. 583084, 2020. DOI: https://doi.org/10.3389/fimmu.2020.583084
RASKOV, Hans et al. Neutrophils and polymorphonuclear myeloid-derived suppressor cells: an emerging battleground in cancer therapy. Oncogenesis, v. 11, n. 1, p. 22, 2022. DOI: https://doi.org/10.1038/s41389-022-00398-3
RÉBÉ, Cédric; GHIRINGHELLI, François. Interleukin-1β and cancer. Cancers, v. 12, n. 7, p. 1791, 2020. DOI: https://doi.org/10.3390/cancers12071791
SEKHOACHA, Mamello et al. Prostate cancer review: genetics, diagnosis, treatment options, and alternative approaches. Molecules, v. 27, n. 17, p. 5730, 2022. DOI: https://doi.org/10.3390/molecules27175730
SHAUL, Merav E.; FRIDLENDER, Zvi G. Tumour-associated neutrophils in patients with cancer. Nature reviews Clinical oncology, v. 16, n. 10, p. 601-620, 2019. DOI: https://doi.org/10.1038/s41571-019-0222-4
SIEMIŃSKA, Izabela; BARAN, Jarek. Myeloid-derived suppressor cells as key players and promising therapy targets in prostate cancer. Frontiers in Oncology, v. 12, p. 862416, 2022. DOI: https://doi.org/10.3389/fonc.2022.862416
SILVA, Estela Vieira de Souza et al. Elucidating tumor immunosurveillance and immunoediting: a comprehensive review. Ciência Animal Brasileira, v. 22, p. e-68544, 2021. DOI: https://doi.org/10.1590/1809-6891v22e-68544
SUAREZ‐CARMONA, Meggy et al. EMT and inflammation: inseparable actors of cancer progression. Molecular oncology, v. 11, n. 7, p. 805-823, 2017. DOI: https://doi.org/10.1002/1878-0261.12095
STULTZ, Jacob; FONG, Lawrence. How to turn up the heat on the cold immune microenvironment of metastatic prostate cancer. Prostate cancer and prostatic diseases, v. 24, n. 3, p. 697-717, 2021. DOI: https://doi.org/10.1038/s41391-021-00340-5
TAKASUGI, Masaki; YOSHIDA, Yuya; OHTANI, Naoko. Cellular senescence and the tumour microenvironment. Molecular oncology, v. 16, n. 18, p. 3333-3351, 2022. DOI: https://doi.org/10.1002/1878-0261.13268
THOMPSON-ELLIOTT, Bethtrice; JOHNSON, Rarnice; KHAN, Shafiq A. Alterations in TGFβ signaling during prostate cancer progression. American journal of clinical and experimental urology, v. 9, n. 4, p. 318, 2021.
URIBE-QUEROL, Eileen; ROSALES, Carlos. Neutrophils in cancer: two sides of the same coin. Journal of immunology research, v. 2015, n. 1, p. 983698, 2015. DOI: https://doi.org/10.1155/2015/983698
WANG, Yutao; CHEN, Yiming; WANG, Jianfeng. Role of Tumor Microenvironment in Prostate Cancer Immunometabolism. Biomolecules, v. 15, n. 6, p. 826, 2025. DOI: https://doi.org/10.3390/biom15060826
WANG, Yutao; CHEN, Yiming; WANG, Jianfeng. Targeting the tumor microenvironment, a new therapeutic approach for prostate cancer. [S.l.]: [s.n.], 2024.
WASIM, Sobia; LEE, Sang-Yoon; KIM, Jaehong. Complexities of prostate cancer. International journal of molecular sciences, v. 23, n. 22, p. 14257, 2022. DOI: https://doi.org/10.3390/ijms232214257
WYLIE, Ben et al. Dendritic cells and cancer: from biology to therapeutic intervention. Cancers, v. 11, n. 4, p. 521, 2019. DOI: https://doi.org/10.3390/cancers11040521
XIA, Haoran et al. Identification of a hypoxia-related gene signature for predicting systemic metastasis in prostate cancer. Frontiers in Cell and Developmental Biology, v. 9, p. 696364, 2021. DOI: https://doi.org/10.3389/fcell.2021.696364
ZITVOGEL, Laurence et al. Microbiome and anticancer immunosurveillance. Cell, v. 165, n. 2, p. 276-287, 2016. DOI: https://doi.org/10.1016/j.cell.2016.03.001
