Author:
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
Abstract
Abstract
Background
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.
Methods
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).
Results
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).
Conclusions
These findings support the potential role of crosstalk between pro-inflammatory Mφ and cytotoxic T cells in the clinical benefit of tislelizumab.
Trial registration
NCT02407990, NCT04068519, NCT04004221.
Publisher
Springer Science and Business Media LLC
Subject
Biochemistry (medical),Clinical Biochemistry,Molecular Medicine
Cited by
2 articles.
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