T-cell immunotherapy is now a first-line cancer treatment for metastatic melanoma and some lung cancer subtypes, which is a welcome clinical success. However, the response rates observed in these diseases are not yet replicated across other prominent solid tumour types, particularly stromal-rich subtypes with a complex microenvironment that suppresses infiltrating T cells. Cancer-associated fibroblasts (CAFs) are one of the most abundant and pro-pathogenic players in the tumour microenvironment, promoting tumour neogenesis, persistence and metastasis. Accumulating evidence is clear that CAFs subdue anti-tumour T-cell immunity and interfere with immunotherapy. CAFs can be grouped into different subtypes that operate synergistically to suppress T-cell function, including myofibroblastic CAFs, inflammatory CAFs and antigen-presenting CAFs, among other nomenclatures. Here, we review the mechanisms used by CAFs to induce T- cell tolerance and how these functions are likely to affect immunotherapy outcomes.

中文翻译：

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肿瘤成纤维细胞亚群差异诱导 T 细胞耐受

T细胞免疫疗法现已成为转移性黑色素瘤和某些肺癌亚型的一线癌症治疗方法，在临床上取得了可喜的成功。然而，在这些疾病中观察到的反应率尚未在其他主要实体瘤类型中复制，特别是具有抑制浸润性 T 细胞的复杂微环境的富含基质的亚型。癌症相关成纤维细胞（CAF）是肿瘤微环境中最丰富且促致病的细胞之一，促进肿瘤新生、持续存在和转移。越来越多的证据明确表明，CAF 会抑制抗肿瘤 T 细胞免疫并干扰免疫治疗。 CAF 可分为不同的亚型，这些亚型协同作用以抑制 T 细胞功能，包括肌纤维母细胞 CAF、炎症性 CAF 和抗原呈递 CAF 等。在这里，我们回顾了 CAF 用于诱导 T 细胞耐受的机制以及这些功能如何影响免疫治疗结果。