肿瘤微环境
免疫疗法
炎症
癌症研究
效应器
巨噬细胞极化
医学
免疫系统
巨噬细胞
免疫学
生物
体外
生物化学
作者
Jiashu Han,Lei Dong,Mei Wu,Fei Ma
标识
DOI:10.3389/fimmu.2023.1160340
摘要
Immunotherapy has brought a paradigm shift in the treatment of tumors in recent decades. However, a significant proportion of patients remain unresponsive, largely due to the immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages (TAMs) play crucial roles in shaping the TME by exhibiting dual identities as both mediators and responders of inflammation. TAMs closely interact with intratumoral T cells, regulating their infiltration, activation, expansion, effector function, and exhaustion through multiple secretory and surface factors. Nevertheless, the heterogeneous and plastic nature of TAMs renders the targeting of any of these factors alone inadequate and poses significant challenges for mechanistic studies and clinical translation of corresponding therapies. In this review, we present a comprehensive summary of the mechanisms by which TAMs dynamically polarize to influence intratumoral T cells, with a focus on their interaction with other TME cells and metabolic competition. For each mechanism, we also discuss relevant therapeutic opportunities, including non-specific and targeted approaches in combination with checkpoint inhibitors and cellular therapies. Our ultimate goal is to develop macrophage-centered therapies that can fine-tune tumor inflammation and empower immunotherapy.
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