Application status and prospects of single-cell sequencing technology in immunotherapy of prostate cancer

doi:10.3877/cma.j.issn.1674-3253.2025.04.018

Abstract

Abstract:

Prostate cancer is one of the most common malignancies in men and the current standard treatment for metastatic prostate cancer is androgen deprivation therapy. However, the patients treated with androgen deprivation therapy eventually develop metastatic castration-resistant prostate cancer. Immunotherapy has shown promising results in a variety of tumors, but in prostate cancer, the results have been less than satisfactory. Single-cell sequencing technology enables high-resolution analysis of cells at the single-cell level, which is of great value for studying immunotherapy for prostate cancer. This article reviews the research status and future development of single-cell sequencing technology in the immunotherapy of prostate cancer.

Key words: Single-cell sequencing, Prostate cancer, Immunotherapy, Tumor microenvironment, Immune checkpoints

Tingwu Tan, Pingxin Zhang, Chengxing Xia, Delin Yang. Application status and prospects of single-cell sequencing technology in immunotherapy of prostate cancer[J]. Chinese Journal of Endourology(Electronic Edition), 2025, 19(04): 508-513.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhqjmnmwkzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-3253.2025.04.018

https://zhqjmnmwkzz.cma-cmc.com.cn/EN/Y2025/V19/I04/508

References 48

[1]	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.
[2]	Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023[J]. CA A Cancer J Clin, 2023, 73(1): 17-48. DOI: 10.3322/caac.21763.
[3]	He H, Liang L, Han D, et al. Different trends in the incidence and mortality rates of prostate cancer between China and the USA: a joinpoint and age-period-cohort analysis[J]. Front Med (Lausanne), 2022, 9: 824464. DOI: 10.3389/fmed.2022.824464.
[4]	Shi W, Wang Y, Zhao Y, et al. Immune checkpoint B7-H3 is a therapeutic vulnerability in prostate cancer harboring PTEN and TP53 deficiencies[J]. Sci Transl Med, 2023, 15(695): eadf6724. DOI: 10.1126/scitranslmed.adf6724.
[5]	Yasen A, Aini A, Wang H, et al. Progress and applications of single-cell sequencing techniques[J]. Infect Genet Evol, 2020, 80: 104198. DOI: 10.1016/j.meegid.2020.104198.
[6]	Tang X, Huang Y, Lei J, et al. The single-cell sequencing: new developments and medical applications[J]. Cell Biosci, 2019, 9: 53. DOI: 10.1186/s13578-019-0314-y.
[7]	方雯, 孙洋. 单细胞技术在药理学研究中的应用[J]. 中国药理学通报, 2023, 39(9): 1601-1606, 1612. DOI: 10.12360/CPB202302072.
[8]	冉志强, 桂定文. 系统免疫炎症指数与前列腺癌相关性的研究进展[J]. 现代泌尿生殖肿瘤杂志, 2024, 16(5): 317-320. DOI: 10.3870/j.issn.1674-4624.2023.05.016.
[9]	Chen S, Zhu G, Yang Y, et al. Single-cell analysis reveals transcriptomic remodellings in distinct cell types that contribute to human prostate cancer progression[J]. Nat Cell Biol, 2021, 23(1): 87-98. DOI: 10.1038/s41556-020-00613-6.
[10]	Tuong ZK, Loudon KW, Berry B, et al. Resolving the immune landscape of human prostate at a single-cell level in health and cancer[J]. Cell Rep, 2021, 37(12): 110132. DOI: 10.1016/j.celrep.2021.110132.
[11]	Zhang Y, Fan A, Li Y, et al. Single-cell RNA sequencing reveals that HSD17B2 in cancer-associated fibroblasts promotes the development and progression of castration-resistant prostate cancer[J]. Cancer Lett, 2023, 566: 216244. DOI: 10.1016/j.canlet.2023.216244.
[12]	Siefert JC, Cioni B, Muraro MJ, et al. The prognostic potential of human prostate cancer-associated macrophage subtypes as revealed by single-cell transcriptomics[J]. Mol Cancer Res, 2021, 19(10): 1778-1791. DOI: 10.1158/1541-7786.MCR-20-0740.
[13]	Abbott M, Ustoyev Y. Cancer and the immune system: the history and background of immunotherapy[J]. Semin Oncol Nurs, 2019, 35(5): 150923. DOI: 10.1016/j.soncn.2019.08.002.
[14]	Patel D, McKay R, Kellogg Parsons J. Immunotherapy for localized prostate cancer: the next frontier?[J]. Urol Clin North Am, 2020, 47(4): 443-456. DOI: 10.1016/j.ucl.2020.07.008.
[15]	Gulley JL, Borre M, Vogelzang NJ, et al. Phase III trial of PROSTVAC in asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer[J]. J Clin Oncol, 2019, 37(13): 1051-1061. DOI: 10.1200/JCO.18.02031.
[16]	Bagchi S, Yuan R, Engleman EG. Immune checkpoint inhibitors for the treatment of cancer: clinical impact and mechanisms of response and resistance[J]. Annu Rev Pathol, 2021, 16: 223-249. DOI: 10.1146/annurev-pathol-042020-042741.
[17]	Pan J, Ma Z, Liu B, et al. Identification of cancer-associated fibroblasts subtypes in prostate cancer[J]. Front Immunol, 2023, 14: 1133160. DOI: 10.3389/fimmu.2023.1133160.
[18]	Zhao D, Cai L, Lu X, et al. Chromatin regulator CHD1 remodels the immunosuppressive tumor microenvironment in PTEN-deficient prostate cancer[J]. Cancer Discov, 2020, 10(9): 1374-1387. DOI: 10.1158/2159-8290.CD-19-1352.
[19]	Wu F, Ning H, Sun Y, et al. Integrative exploration of the mutual gene signatures and immune microenvironment between benign prostate hyperplasia and castration-resistant prostate cancer[J]. Aging Male, 2023, 26(1): 2183947. DOI: 10.1080/13685538.2023.2183947.
[20]	Nickols NG, Ganapathy E, Nguyen C, et al. The intraprostatic immune environment after stereotactic body radiotherapy is dominated by myeloid cells[J]. Prostate Cancer Prostatic Dis, 2021, 24(1): 135-139. DOI: 10.1038/s41391-020-0249-8.
[21]	Chaudagar K, Hieromnimon HM, Khurana R, et al. Reversal of lactate and PD-1-mediated macrophage immunosuppression controls growth of PTEN/p53-deficient prostate cancer[J]. Clin Cancer Res, 2023, 29(10): 1952-1968. DOI: 10.1158/1078-0432.CCR-22-3350.
[22]	Murphy S, Rahmy S, Gan D, et al. Overcome prostate cancer resistance to immune checkpoint therapy with ketogenic diet-induced epigenetic reprogramming[J]. bioRxiv, 2023: 2023.08.07.552383. DOI: 10.1101/2023.08.07.552383.
[23]	Peng S, Hu P, Xiao YT, et al. Single-cell analysis reveals EP4 as a target for restoring T-cell infiltration and sensitizing prostate cancer to immunotherapy[J]. Clin Cancer Res, 2022, 28(3): 552-567. DOI: 10.1158/1078-0432.CCR-21-0299.
[24]	Hawley JE, Obradovic AZ, Dallos MC, et al. Anti-PD-1 immunotherapy with androgen deprivation therapy induces robust immune infiltration in metastatic castration-sensitive prostate cancer[J]. Cancer Cell, 2023, 41(11): 1972-1988.e5. DOI: 10.1016/j.ccell.2023.10.006.
[25]	Song H, Lu T, Han D, et al. YAP1 inhibition induces phenotype switching of cancer-associated fibroblasts to tumor suppressive in prostate cancer[J]. Cancer Res, 2024, 84(22): 3728-3742. DOI: 10.1158/0008-5472.CAN-24-0932.
[26]	Xin S, Liu X, Li Z, et al. ScRNA-seq revealed an immunosuppression state and tumor microenvironment heterogeneity related to lymph node metastasis in prostate cancer[J]. Exp Hematol Oncol, 2023, 12(1): 49. DOI: 10.1186/s40164-023-00407-0.
[27]	Wang J, Wu W, Yuan T, et al. Tumor-associated macrophages and PD-L1 in prostate cancer: a possible key to unlocking immunotherapy efficacy[J]. Aging (Albany NY), 2024, 16(1): 445-465. DOI: 10.18632/aging.205378.
[28]	Wang X, Ma L, Pei X, et al. Comprehensive assessment of cellular senescence in the tumor microenvironment[J]. Brief Bioinform, 2022, 23(3): bbac118. DOI: 10.1093/bib/bbac118.
[29]	Adorno Febles VR, Hao Y, Ahsan A, et al. Single-cell analysis of localized prostate cancer patients links high Gleason score with an immunosuppressive profile[J]. Prostate, 2023, 83(9): 840-849. DOI: 10.1002/pros.24524.
[30]	Lyu F, Gao X, Ma M, et al. Crafting a personalized prognostic model for malignant prostate cancer patients using risk gene signatures discovered through TCGA-PRAD mining, machine learning, and single-cell RNA-sequencing[J]. Diagnostics (Basel), 2023, 13(12): 1997. DOI: 10.3390/diagnostics13121997.
[31]	Liu W, Wang M, Wang M, et al. Single-cell and bulk RNA sequencing reveal cancer-associated fibroblast heterogeneity and a prognostic signature in prostate cancer[J]. Medicine (Baltimore), 2023, 102(32): e34611. DOI: 10.1097/MD.0000000000034611.
[32]	Chen C, Luo J, Wang X. Identification of prostate cancer subtypes based on immune signature scores in bulk and single-cell transcriptomes[J]. Med Oncol, 2022, 39(9): 123. DOI: 10.1007/s12032-022-01719-7.
[33]	Li X, Zheng C, Xue X, et al. Integrated analysis of single-cell and bulk RNA sequencing identifies a signature based on macrophage marker genes involved in prostate cancer prognosis and treatment responsiveness[J]. Funct Integr Genomics, 2023, 23(2): 115. DOI: 10.1007/s10142-023-01037-9.
[34]	Zhang J, Li Z, Chen Z, et al. Comprehensive analysis of macrophage-related genes in prostate cancer by integrated analysis of single-cell and bulk RNA sequencing[J]. Aging (Albany NY), 2024, 16(8): 6809-6838. DOI: 10.18632/aging.205727.
[35]	Gao Z, Zhang N, An B, et al. Comprehensive analyses of the cancer-associated fibroblast subtypes and their score system for prediction of outcomes and immunosuppressive microenvironment in prostate cancer[J]. Cancer Cell Int, 2024, 24(1): 127. DOI: 10.1186/s12935-024-03305-5.
[36]	Li Q, Zhu J, Zhang Y, et al. Association of WHSC1/NSD2 and T-cell infiltration with prostate cancer metastasis and prognosis[J]. Sci Rep, 2023, 13(1): 21629. DOI: 10.1038/s41598-023-48906-8.
[37]	Wang Q, Feng C, Chen Y, et al. Evaluation of CD47 in the suppressive tumor microenvironment and immunotherapy in prostate cancer[J]. J Immunol Res, 2023, 2023: 2473075. DOI: 10.1155/2023/2473075.
[38]	Liang H, Zhang L, Liu Z, et al. Upregulation of TLR5 indicates a favorable prognosis in prostate cancer[J]. Prostate, 2023, 83(11): 1035-1045. DOI: 10.1002/pros.24545.
[39]	Wong HY, Sheng Q, Hesterberg AB, et al. Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease[J]. Nat Commun, 2022, 13(1): 6036. DOI: 10.1038/s41467-022-33780-1.
[40]	De Vargas Roditi L, Jacobs A, Rueschoff JH, et al. Single-cell proteomics defines the cellular heterogeneity of localized prostate cancer[J]. Cell Rep Med, 2022, 3(4): 100604. DOI: 10.1016/j.xcrm.2022.100604.
[41]	Tshering LF, Luo F, Russ S, et al. Immune mechanisms shape the clonal landscape during early progression of prostate cancer[J]. Dev Cell, 2023, 58(12): 1071-1086.e8. DOI: 10.1016/j.devcel.2023.04.010.
[42]	Bilusic M, Madan RA, Gulley JL. Immunotherapy of prostate cancer: facts and hopes[J]. Clin Cancer Res, 2017, 23(22): 6764-6770. DOI: 10.1158/1078-0432.CCR-17-0019.
[43]	朱孝仁, 陈敏斌, 姜鉴倬, 等.基于单细胞测序探究去势抵抗性前列腺癌肿瘤微环境及细胞间通讯相关信号分子[J].江苏大学学报(医学版), 2024, 34(6): 497-506. DOI: 10.13312/j.issn.1671-7783.y240003.
[44]	Zhu W, Zeng H, Huang J, et al. Integrated machine learning identifies epithelial cell marker genes for improving outcomes and immunotherapy in prostate cancer[J]. J Transl Med, 2023, 21(1): 782. DOI: 10.1186/s12967-023-04633-2.
[45]	Miao M, Song Y, Jin M, et al. Single-cell RNA combined with bulk RNA analysis to explore oxidative stress and energy metabolism factors and found a new prostate cancer oncogene MXRA8[J]. Aging (Albany NY), 2024, 16(5): 4469-4502. DOI: 10.18632/aging.205599.
[46]	Wen XY, Wang RY, Yu B, et al. Integrating single-cell and bulk RNA sequencing to predict prognosis and immunotherapy response in prostate cancer[J]. Sci Rep, 2023, 13(1): 15597. DOI: 10.1038/s41598-023-42858-9.
[47]	Li T, Zhou Z, Xie Z, et al. Identification and validation of cancer-associated fibroblast-related subtypes and the prognosis model of biochemical recurrence in prostate cancer based on single-cell and bulk RNA sequencing[J]. J Cancer Res Clin Oncol, 2023, 149(13): 11379-11395. DOI: 10.1007/s00432-023-05011-7.
[48]	Zhang X, Hong B, Sun Z, et al. Development and validation of a circulating tumor cells-related signature focusing on biochemical recurrence and immunotherapy response in prostate cancer[J]. Heliyon, 2023, 9(12): e22648. DOI: 10.1016/j.heliyon.2023.e22648.

Please choose a citation manager

Content to export