Document Type : Original Article
Authors
1 Department of Genetics, Kaz.C., Islamic Azad University, Kazerun, Iran
2 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
3 Department of Biology, Zand Institute of Higher Education, Shiraz, Iran
4 Department of Biology, Kaz.C., Islamic Azad University, Kazerun, Iran
Abstract
Introduction: Bicalutamide, an antiandrogen agent used in prostate cancer treatment, has been shown to influence immune cells and alter the immune response within the tumor microenvironment. This study investigated the impact of bicalutamide on the expression patterns of immune checkpoints in dendritic cells.
Methods: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) were utilized to differentiate monocytes isolated from peripheral blood mononuclear cells into immature dendritic cells (iDCs). Subsequently, prostate cancer cell lysates were employed to treat iDCs in order to facilitate their maturation into mature dendritic cells (mDCs). Bicalutamide treatment was then applied to the mDCs, followed by total RNA extraction. After cDNA synthesis, the expression of inhibitory immune checkpoints was analyzed using quantitative real-time PCR (qPCR).
Results: The findings indicated that administration of Bicalutamide to mDCs significantly decreased the mRNA expression levels of several inhibitory immune checkpoints, including B- and T-lymphocyte attenuator (BTLA), V-domain Ig suppressor of T cell activation (VISTA), lymphocyte-activation gene 3 (LAG-3), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and programmed-death ligand 1 (PD-L1).
Conclusion: The findings suggested that bicalutamide might exert an immunomodulatory effect on dendritic cells and possess the potential for consideration in DC-mediated immunotherapies for prostate cancer.
Keywords
- Berenguer CV, Pereira F, Camara JS, Pereira JAM. Underlying features of prostate cancer—statistics, risk factors, and emerging methods for its diagnosis. Curr Oncol. 2023;30(2):2300-21.
- Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12-49.
- Posdzich P, Darr C, Hilser T, Wahl M, Herrmann K, Hadaschik B, et al. Metastatic prostate cancer—a review of current treatment options and promising new approaches. Cancers (Basel). 2023;15(2):461.
- Kim SK, Cho SW. The evasion mechanisms of cancer immunity and drug intervention in the tumor microenvironment. Front Pharmacol. 2022;13:868695.
- Raskov H, Orhan A, Christensen JP, Gogenur I. Cytotoxic CD8(+) T cells in cancer and cancer immunotherapy. Br J Cancer. 2021;124(2):359-67.
- Kobayashi Y, Lim SO, Yamaguchi H. Oncogenic signaling pathways associated with immune evasion and resistance to immune checkpoint inhibitors in cancer. Semin Cancer Biol. 2020;65:51-64.
- Han Y, Liu D, Li L. PD-1/PD-L1 pathway: current researches in cancer. Am J Cancer Res. 2020;10(3):727-42.
- Qin S, Xu L, Yi M, Yu S, Wu K, Luo S. Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4. Mol Cancer. 2019;18(1):155.
- Guo Z, Zhang R, Yang AG, Zheng G. Diversity of immune checkpoints in cancer immunotherapy. Front Immunol. 2023;14:1121285.
- Song L, Dong G, Guo L, Graves DT. The function of dendritic cells in modulating the host response. Mol Oral Microbiol. 2018;33(1):13-21.
- Marciscano AE, Anandasabapathy N. The role of dendritic cells in cancer and anti-tumor immunity. Semin Immunol. 2021;52:101481.
- Shabbir S, Khurram E, Moorthi VS, Eissa YTH, Kamal MA, Butler AE. The interplay between androgens and the immune response in polycystic ovary syndrome. J Transl Med. 2023;21(1):259.
- Nourbakhsh NS, Naeimi S, Moghanibashi M, Baradaran B. Bicalutamide reveals immunomodulatory effects in prostate cancer by regulating immunogenic dendritic cell maturation. Tissue Cell. 2024;91:102530.
- Del Prete A, Salvi V, Soriani A, Laffranchi M, Sozio F, Bosisio D, et al. Dendritic cell subsets in cancer immunity and tumor antigen sensing. Cell Mol Immunol. 2023;20(5):432-47.
- Wang Y, Xiang Y, Xin VW, Wang XW, Peng XC, Liu XQ, et al. Dendritic cell biology and its role in tumor immunotherapy. J Hematol Oncol. 2020;13(1):107.
- Ghorbaninezhad F, Asadzadeh Z, Masoumi J, Mokhtarzadeh A, Kazemi T, Aghebati-Maleki L, et al. Dendritic cell-based cancer immunotherapy in the era of immune checkpoint inhibitors: from bench to bedside. Life Sci. 2022;297:120466.
- Wang T, Alavian MR, Goel HL, Languino LR, Fitzgerald TJ. Bicalutamide inhibits androgen-mediated adhesion of prostate cancer cells exposed to ionizing radiation. Prostate. 2008;68(16):1734-42.
- Bonifazi F, Pavoni C, Peccatori J, Giglio F, Arpinati M, Busca A, et al. Myeloablative conditioning with thiotepa-busulfan-fludarabine does not improve the outcome of patients transplanted with active leukemia: final results of the GITMO prospective trial GANDALF-01. Bone Marrow Transplant. 2022;57(6):949-58.
- Peng Q, Qiu X, Zhang Z, Zhang S, Zhang Y, Liang Y, et al. PD-L1 on dendritic cells attenuates T cell activation and regulates response to immune checkpoint blockade. Nat Commun. 2020;11(1):4835.
- Oh SA, Wu DC, Cheung J, Navarro A, Xiong H, Cubas R, et al. PD-L1 expression by dendritic cells is a key regulator of T-cell immunity in cancer. Nat Cancer. 2020;1(7):681-91.
- Palicelli A, Bonacini M, Croci S, Bisagni A, Zanetti E, De Biase D, et al. What do we have to know about PD-L1 expression in prostate cancer? A systematic literature review. Part 7: PD-L1 expression in liquid biopsy. J Pers Med. 2021;11(12):1312.
- Wang XB, Fan ZZ, Anton D, Vollenhoven AV, Ni ZH, Chen XF, et al. CTLA4 is expressed on mature dendritic cells derived from human monocytes and influences their maturation and antigen presentation. BMC Immunol. 2011;12:21.
- Li R, Qiu J, Zhang Z, Qu C, Tang Z, Yu W, et al. Prognostic significance of Lymphocyte-activation gene 3 (LAG3) in patients with solid tumors: a systematic review, meta-analysis and pan-cancer analysis. Cancer Cell Int. 2023;23(1):306.
- Andrews LP, Cillo AR, Karapetyan L, Kirkwood JM, Workman CJ, Vignali DAA. Molecular pathways and mechanisms of LAG3 in cancer therapy. Clin Cancer Res. 2022;28(23):5030-9.
- Zhang JA, Lu YB, Wang WD, Liu GB, Chen C, Shen L, et al. BTLA-expressing dendritic cells in patients with tuberculosis exhibit reduced production of IL-12/IFN-alpha and increased production of IL-4 and TGF-beta, favoring Th2 and Foxp3(+) Treg polarization. Front Immunol. 2020;11:518.
- Shekari N, Shanehbandi D, Kazemi T, Zarredar H, Baradaran B, Jalali SA. VISTA and its ligands: the next generation of promising therapeutic targets in immunotherapy. Cancer Cell Int. 2023;23(1):265.
)