CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Targeting TREM2 on tumor-associated macrophages enhances immunotherapy.
Targeting TREM2 on tumor-associated macrophages enhances immunotherapy.
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将检查点抑制剂（CPI）耐药个体转化为应答者需要识别抑制性机制。我们发现，在小鼠同系肿瘤模型和多种组织学类型的人类实体瘤中，TREM2+ 肿瘤相关巨噬细胞（TAM）与耗竭的 CD8+ TIL（肿瘤浸润淋巴细胞）相关。Fc 结构域增强的抗 TREM2 单克隆抗体（mAb）治疗通过消除和调节 TAM 群体促进抗肿瘤免疫，从而导致 CD8+ TIL 浸润和效应功能增强。TREM2+ TAM 在卵巢癌个体中最为富集，其中 TREM2 表达与疾病分级相对应，并伴有更差的无复发生存期。在侵袭性原位卵巢癌模型中，抗 TREM2 mAb 治疗驱动了强效的抗肿瘤免疫。这些结果突出表明，对于对 CPI 治疗无应答且可能具有 TAM 丰富肿瘤微环境的个体，TREM2 是一个极具吸引力的免疫治疗调节靶点。
Converting checkpoint inhibitor (CPI)-resistant individuals to being responsive requires identifying suppressive mechanisms.
We identify TREM2 + tumor-associated macrophages (TAMs) as being correlated with exhausted CD8 + tumor-infiltrating lymphocytes (TILs) in mouse syngeneic tumor models and human solid tumors of multiple histological types. Fc domain-enhanced anti-TREM2 monoclonal antibody (mAb) therapy promotes anti-tumor immunity by elimination and modulation of TAM populations, which leads to enhanced CD8 + TIL infiltration and effector function.
TREM2 + TAMs are most enriched in individuals with ovarian cancer, where TREM2 expression corresponds to disease grade accompanied by worse recurrence-free survival. In an aggressive orthotopic ovarian cancer model, anti-TREM2 mAb therapy drives potent anti-tumor immunity. These results highlight TREM2 as a highly attractive target for immunotherapy modulation in individuals who are refractory to CPI therapy and likely have a TAM-rich tumor microenvironment.
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