Co-enrichment of CD8-positive T cells and macrophages is associated with clinical benefit of tislelizumab in solid tumors

Ye, D; Desai, J; Shi, J; Liu, SM; Shen, W; Liu, T; Shi, Y; Wang, D; Liang, L; Yang, S; Ma, X; Jin, W; Zhang, P; Huang, R; Shen, Z; Zhang, Y; Wu, YL

Author(s): Ye, D; Desai, J; Shi, J; Liu, SM; Shen, W; Liu, T; Shi, Y; Wang, D; Liang, L; Yang, S; Ma, X; Jin, W; Zhang, P; Huang, R; Shen, Z; Zhang, Y; Wu, YL;
Details: Publication Year 2023-03-07,Volume 11,Issue #1,Page 25
Journal Title: Biomarker Research
Publication Type: Research article
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 (Mphi) 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 Mphi 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 Mphi was coupled with elevated CD8(+) T-cell cytotoxicity, T-cell trafficking, MHC class I antigen presentation signatures/genes, and enrichment of the pro-inflammatory Mphi polarization pathway. Additionally, a high level of pro-inflammatory CD64(+) Mphi 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(+) Mphi 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 Mphi and cytotoxic T cells in the clinical benefit of tislelizumab. TRIAL REGISTRATION: NCT02407990, NCT04068519, NCT04004221.
Publisher: BioMed Central
Keywords: Immune cells; Immunotherapy; Macrophages; Tislelizumab; Tumor microenvironment
Department(s): Medical Oncology
PubMed ID: 36879284
Publisher's Version: https://doi.org/10.1186/s40364-023-00465-w
Open Access at Publisher's Site: https://doi.org/10.1186/s40364-023-00465-w
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-07-11 06:23:42

Last Modified: 2023-07-11 06:25:37