Department of Pathology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California, USA.
Clin Exp Med. 2023 Dec;23(8):4289-4296. doi: 10.1007/s10238-023-01240-9. Epub 2023 Nov 1.
Cancer immunotherapy, particularly immune checkpoint inhibitors, has opened a new avenue for cancer treatment following the durable clinical benefits. Despite the clinical successes across several cancer types, primary or acquired resistance might eventually lead to cancer progression in patients with clinical responses. Hence, to broaden the clinical applicability of these treatments, a detailed understanding of the mechanisms limiting the efficacy of cancer immunotherapy is needed. Evidence provided thus far has implicated immunosuppressive innate immune cells infiltrating the tumor microenvironment as key players in immunotherapy resistance. According to the available data, genetic alterations can shape the innate immune response to promote immunotherapy resistance and tumor progression. Herein, this review has discussed the current understanding of the underlying mechanisms where genetic alterations modulate the innate immune milieu to drive immunosuppression and immunotherapy resistance.
癌症免疫疗法，特别是免疫检查点抑制剂，在带来持久的临床获益后，为癌症治疗开辟了新途径。尽管在多种癌症类型中取得了临床成功，但原发性或获得性耐药最终可能导致有临床反应的患者癌症进展。因此，为了扩大这些治疗方法的临床适用性，需要深入了解限制癌症免疫疗法疗效的机制。迄今为止提供的证据表明，浸润肿瘤微环境的免疫抑制性固有免疫细胞是免疫治疗耐药的关键因素。根据现有数据，遗传改变可以塑造固有免疫反应，以促进免疫治疗耐药和肿瘤进展。本文讨论了目前对遗传改变调节固有免疫环境以驱动免疫抑制和免疫治疗耐药的潜在机制的理解。
