The Immunotherapy and Immunosuppressive Signaling in Therapy-Resistant Prostate Cancer.
The Immunotherapy and Immunosuppressive Signaling in Therapy-Resistant Prostate Cancer.
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DOI：
10.3390/biomedicines10081778
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发表时间：
2022-07-22
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
前列腺癌是男性最常见的恶性肿瘤之一。最初，它是雄激素依赖性的，但最终发展为去势抵抗性前列腺癌（CRPC），目前雄激素受体信号靶向治疗和化疗是无法治愈的。免疫疗法，特别是免疫检查点抑制剂，为治疗这种类型的前列腺癌带来了希望。疫苗、过继性嵌合抗原受体- t （CAR-T）细胞和免疫检查点抑制剂等方法已被用于激活先天和适应性免疫反应来治疗前列腺癌，但成功率有限。只有Sipuleucel-T和免疫检查点抑制剂pembrolizumab被美国FDA批准用于治疗有限的前列腺癌患者。前列腺癌是一个复杂的肿瘤微环境（tumor microenvironment， TME），多种免疫抑制分子和机制共存并相互作用。此外，前列腺癌被认为是一种“冷”肿瘤，肿瘤突变负荷低，抗原呈递和细胞毒性t细胞激活量低，免疫抑制分子（包括细胞因子/趋化因子）水平高。因此，了解免疫抑制信号激活和免疫逃避的机制将有助于开发更有效的前列腺癌治疗方法。本文综述了前列腺癌免疫治疗的最新进展，重点介绍了前列腺癌免疫逃避的分子机制。同时，我们也突出了一些潜在的治疗靶点，为前列腺癌的治疗提供理论依据。
Prostate cancer is one of the most common malignant tumors in men. Initially, it is androgen-dependent, but it eventually develops into castration-resistant prostate cancer (CRPC), which is incurable with current androgen receptor signaling target therapy and chemotherapy. Immunotherapy, specifically with immune checkpoint inhibitors, has brought hope for the treatment of this type of prostate cancer. Approaches such as vaccines, adoptive chimeric antigen receptor-T (CAR-T) cells, and immune checkpoint inhibitors have been employed to activate innate and adaptive immune responses to treat prostate cancer, but with limited success. Only Sipuleucel-T and the immune checkpoint inhibitor pembrolizumab are approved by the US FDA for the treatment of limited prostate cancer patients. Prostate cancer has a complex tumor microenvironment (TME) in which various immunosuppressive molecules and mechanisms coexist and interact. Additionally, prostate cancer is considered a “cold” tumor with low levels of tumor mutational burden, low amounts of antigen-presenting and cytotoxic T-cell activation, and high levels of immunosuppressive molecules including cytokines/chemokines. Thus, understanding the mechanisms of immunosuppressive signaling activation and immune evasion will help develop more effective treatments for prostate cancer. The purpose of this review is to summarize emerging advances in prostate cancer immunotherapy, with a particular focus on the molecular mechanisms that lead to immune evasion in prostate cancer. At the same time, we also highlight some potential therapeutic targets to provide a theoretical basis for the treatment of prostate cancer.
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影响因子：
4.1
作者：
Brea LT;Wang X;Yu J
通讯作者：
Yu J
影响因子：
5.7
作者：
Clermont PL;Lin D;Crea F;Wu R;Xue H;Wang Y;Thu KL;Lam WL;Collins CC;Wang Y;Helgason CD
通讯作者：
Helgason CD
DOI：
10.1056/nejmoa1315815
发表时间：
2014-09-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Antonarakis ES;Lu C;Wang H;Luber B;Nakazawa M;Roeser JC;Chen Y;Mohammad TA;Chen Y;Fedor HL;Lotan TL;Zheng Q;De Marzo AM;Isaacs JT;Isaacs WB;Nadal R;Paller CJ;Denmeade SR;Carducci MA;Eisenberger MA;Luo J
通讯作者：
Luo J
影响因子：
29
作者：
Chatterjee S;Daenthanasanmak A;Chakraborty P;Wyatt MW;Dhar P;Selvam SP;Fu J;Zhang J;Nguyen H;Kang I;Toth K;Al-Homrani M;Husain M;Beeson G;Ball L;Helke K;Husain S;Garrett-Mayer E;Hardiman G;Mehrotra M;Nishimura MI;Beeson CC;Bupp MG;Wu J;Ogretmen B;Paulos CM;Rathmell J;Yu XZ;Mehrotra S
通讯作者：
Mehrotra S
影响因子：
64.5
作者：
Arora VK;Schenkein E;Murali R;Subudhi SK;Wongvipat J;Balbas MD;Shah N;Cai L;Efstathiou E;Logothetis C;Zheng D;Sawyers CL
通讯作者：
Sawyers CL