去势抵抗性前列腺癌免疫微环境的研究现状与治疗方向

杨文博; 张斌; 吴佳慧; 崔洁

doi:10.19401/j.cnki.1007-3639.2023.10.007

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去势抵抗性前列腺癌免疫微环境的研究现状与治疗方向

综述 | 更新时间：2025-12-31

- 去势抵抗性前列腺癌免疫微环境的研究现状与治疗方向
- Current status and treatment direction of the immune microenvironment of castration-resistant prostate cancer
- 中国癌症杂志 2023年33卷第10期页码：945-953
- 作者机构：
  
  1. 西安医学院，陕西西安 710021
  2. 西安医学院第一附属医院全科医学科，陕西西安 710077
- 作者简介：
  
  [ "杨文博（ORCID: 0009-0009-0009-5568），在读硕士研究生，主治医师。" ]
  崔洁（ORCID: 0000-0001-7761-1377），主任医师、硕士研究生导师，西安医学院第一附属医院全科医学科主任。
- 基金信息：
  
  西安市科技计划项目(21YXYJ0128)
- DOI：10.19401/j.cnki.1007-3639.2023.10.007
  中图分类号： R737.25
- 收稿：2023-06-23，
  
  修回：2023-09-12，
  
  纸质出版：2023-10-30
- 稿件说明：
移动端阅览
杨文博, 张斌, 吴佳慧, 等. 去势抵抗性前列腺癌免疫微环境的研究现状与治疗方向[J]. 中国癌症杂志, 2023,33(10):945-953.

Wenbo YANG, Bin ZHANG, Jiahui WU, et al. Current status and treatment direction of the immune microenvironment of castration-resistant prostate cancer[J]. China Oncology, 2023, 33(10): 945-953.
杨文博, 张斌, 吴佳慧, 等. 去势抵抗性前列腺癌免疫微环境的研究现状与治疗方向[J]. 中国癌症杂志, 2023,33(10):945-953. DOI： 10.19401/j.cnki.1007-3639.2023.10.007.

Wenbo YANG, Bin ZHANG, Jiahui WU, et al. Current status and treatment direction of the immune microenvironment of castration-resistant prostate cancer[J]. China Oncology, 2023, 33(10): 945-953. DOI： 10.19401/j.cnki.1007-3639.2023.10.007.

摘要

随着肿瘤免疫学的快速发展，越来越多的研究关注肿瘤微环境中的免疫细胞和信号分子的作用。前列腺癌是全球男性发病率第二的恶性肿瘤。随着我国人口老龄化和筛查率的提高，前列腺癌发病率不断上升。雄激素剥夺治疗（androgen deprivation therapy，ADT）是晚期前列腺癌的主要治疗手段。然而，大多数患者在接受ADT治疗后最终都会进展为去势抵抗性前列腺癌（castration-resistant prostate cancer，CRPC）。CRPC患者的中位生存期一直低于2年，近年来出现了一些新的治疗方法，患者生存率有所提高，但总体预后仍然较差。肿瘤免疫治疗通过激发或重建机体的免疫系统，从而控制和杀伤肿瘤细胞。近年来，免疫治疗进入临床研究并快速发展，展现出强大的治疗潜力，成为继手术、放疗、化疗、靶向治疗后的另一种有效的肿瘤治疗手段。然而，免疫治疗对CRPC患者收效甚微。因此，CRPC的肿瘤免疫微环境（tumor immune microenvironment，TIME）备受众多学者的关注。既往的研究认为，CRPC的免疫浸润一般较少，拥有相对较高的免疫抑制性肿瘤微环境，如T淋巴细胞浸润和活性都比较低，且高表达各种免疫抑制因子，如细胞毒性T淋巴细胞相关抗原4（cytotoxic T lymphocyte-associated antigen-4，CTLA-4）、程序性死亡[蛋白]-1（programmed death-1，PD-1）/程序性死亡[蛋白]配体-1（programmed death ligand-1，PD-L1）等，被认为是免疫学上的“冷”肿瘤。除了自身的免疫抑制机制，CRPC还有着复杂的免疫逃逸机制，如抑制免疫细胞活性，或选择性地表达低免疫原性抗原，从而躲避免疫系统识别。由于CRPC特殊的免疫抑制性肿瘤微环境，单独采取免疫治疗的效果往往不理想，筛选适合的免疫治疗方案成为了提高CRPC患者治疗效果的关键。本文总结了CRPC患者TIME中免疫细胞的作用机制，以及免疫检查点抑制剂联合ADT治疗、化疗、Sipuleucel-T肿瘤疫苗、嵌合抗原受体-T（chimeric antigen receptor-T，CAR-T）细胞治疗、溶瘤病毒治疗，或者免疫检查点抑制剂联合趋化因子受体拮抗剂、酪氨酸激酶抑制剂、多腺苷二磷酸核糖聚合酶[poly(ADP-ribose) polymerase，PARP]抑制剂等治疗方法中免疫细胞及各种细胞因子的相互作用关系。总之，CRPC的TIME非常复杂，免疫治疗仍然面临着许多挑战。但随着技术和研究的进步，一些新的免疫治疗方案正在研究中，相信未来肿瘤免疫治疗会给CRPC患者带来更佳的治疗效果。

Abstract

With the rapid development of cancer immunology

more and more research focuses on the role of immune cells and signaling molecules in the tumor microenvironment. Prostate cancer is the second most common malignant tumor in men globally. With the increase in our population ages and screening rates

the incidence of prostate cancer in China is increasing. Androgen deprivation therapy (ADT) is a primary treatment for late-stage prostate cancer. However

most patients eventually progress to castration-resistant prostate cancer (CRPC) after ADT treatment. The median survival of CRPC patients has been less than two years. Although new treatment methods have emerged in recent years

and patient survival has improved

however

the overall prognosis still remains poor. Tumor immunotherapy works by stimulating or rebuilding the body's immune system to control and kill tumor cells. In recent years

immunotherapy has entered clinical research and rapidly developed into an effective tumor-treatment approach following surgery

radiotherapy

chemotherapy and targeted therapy. However

the effect of immunotherapy on CRPC patients is usually very poor. Therefore

the tumor microenvironment of CRPC has attracted many scholars' attention. Previous studies have suggested that CRPC generally has less immune infiltration

a relatively high immunosuppressive tumor microenvironment

such as low infiltration and activity of T cells

and high expressions of various immunosuppressive factors

such as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4)

programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1)

etc.

which is considered as an immune "cold" tumor. In addition to its own immune-inhibitory mechanisms

CRPC has complex immune evasion mechanisms that suppress immune cell activity or selectively express low immunogenic antigen to evade immune system recognition. Due to the particular immunosuppressive tumor microenvironment of CRPC

the effect of immunotherapy alone is often unsatisfactory. Therefore

the selection of appropriate immunotherapy strategies has become the key to improving the treatment effect of CRPC patients. This review summarized the mechanisms underlying immune cells in the immune microenvironment of CRPC tumors and their interactions with various cytokines in the context of immune checkpoint inhibitor therapy combined with ADT

chemotherapy

Sipuleucel-T tumor vaccines

chimeric antigen receptor-T (CAR-T) cell therapy

oncolytic virus therapy

or in combination with chemokine receptor antagonists

tyrosine kinase inhibitors

poly (ADP-ribose) polymerase (PARP) inhibitors and other treatments. In conclusion

the tumor immune microenvironment of CRPC is highly complex

and immunotherapy still faces many challenges. However

with the progress of technological advancements and research

some new immunotherapy options are being studied

and it is believed that tumor immunotherapy will bring better therapeutic effects to patients with CRPC in the future.

关键词

Keywords

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