Ye Dingwei, Desai Jayesh, Shi Jingwen, Liu Si-Yang Maggie, Shen Wei, Liu Tengfei, Shi Yang, Wang Dan, Liang Liang, Yang Silu, Ma Xiaopeng, Jin Wei, Zhang Pei, Huang Ruiqi, Shen Zhirong, Zhang Yun, Wu Yi-Long
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Medical Oncology, Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Australia.
Biomark Res. 2023 Mar 7;11(1):25. doi: 10.1186/s40364-023-00465-w.
Activated immune cells (IC) in the tumor microenvironment (TME) are critical for anti-tumor efficacy. Greater understanding of the dynamic diversity and crosstalk between IC is needed to clarify their association with immune checkpoint inhibitor efficacy.
Patients from three tislelizumab monotherapy trials in solid tumors (NCT02407990, NCT04068519, NCT04004221) were retrospectively divided into subgroups by CD8 T-cell and macrophage (Mφ) levels, assessed via multiplex immunohistochemistry (mIHC; n = 67) or gene expression profiling (GEP; n = 629).
A trend of longer survival was observed in patients with both high CD8 T-cell and Mφ levels versus other subgroups in the mIHC analysis (P = 0.11), which was confirmed with greater statistical significance in the GEP analysis (P = 0.0001). Co-existence of CD8 T cells and Mφ was coupled with elevated CD8 T-cell cytotoxicity, T-cell trafficking, MHC class I antigen presentation signatures/genes, and enrichment of the pro-inflammatory Mφ polarization pathway. Additionally, a high level of pro-inflammatory CD64 Mφ density was associated with an immune-activated TME and survival benefit with tislelizumab (15.2 vs. 5.9 months for low density; P = 0.042). Spatial proximity analysis revealed that closer proximity between CD8 T cells and CD64 Mφ was associated with a survival benefit with tislelizumab (15.2 vs. 5.3 months for low proximity; P = 0.024).
These findings support the potential role of crosstalk between pro-inflammatory Mφ and cytotoxic T cells in the clinical benefit of tislelizumab.
NCT02407990, NCT04068519, NCT04004221.
肿瘤微环境（TME）中活化的免疫细胞（IC）对于抗肿瘤疗效至关重要。需要更深入了解IC之间的动态多样性和相互作用，以阐明它们与免疫检查点抑制剂疗效的关联。
对三项替雷利珠单抗单药治疗实体瘤试验（NCT02407990、NCT04068519、NCT04004221）的患者，通过多重免疫组织化学（mIHC；n = 67）或基因表达谱分析（GEP；n = 629）评估CD8 T细胞和巨噬细胞（Mφ）水平，将患者回顾性分为亚组。
在mIHC分析中，CD8 T细胞和Mφ水平均高的患者与其他亚组相比，观察到生存时间延长的趋势（P = 0.11），在GEP分析中得到了更显著的统计学证实（P = 0.0001）。CD8 T细胞和Mφ共存与CD8 T细胞细胞毒性增加、T细胞 trafficking、MHC I类抗原呈递特征/基因以及促炎Mφ极化途径的富集相关。此外，高水平的促炎CD64 Mφ密度与免疫激活的TME和替雷利珠单抗的生存获益相关（低密度组为5.9个月，高密度组为15.2个月；P = 0.042）。空间 proximity分析显示，CD8 T细胞与CD64 Mφ之间的 proximity更近与替雷利珠单抗的生存获益相关（低 proximity组为5.3个月，高 proximity组为15.2个月；P = 0.024）。
这些发现支持促炎Mφ与细胞毒性T细胞之间的相互作用在替雷利珠单抗临床获益中的潜在作用。
NCT02407990、NCT04068519、NCT04004221。
