Abstract LB514: CD8 T cells and macrophage abundances associated with clinical benefit of tislelizumab in various tumor types
Authors: Shen Wei , Liu Tengfei , Shi Yang , Shi Jingwen , Wang Dan , Liang Liang , Yang Silu , Ma Xiaopeng , Jin Wei , Zhang Pei , Huang Ruiqi , Zhang Yun , Shen Zhirong 
Published: June 2022

Background: Functionally activated immune cells (ICs) in the tumor microenvironment (TME) are critical to antitumor efficacy. Here, we report association between ICs and the clinical efficacy of tislelizumab (TIS), an anti-programmed cell death protein 1 monoclonal antibody, by examining tumor tissues from various tumor types in three pooled Phase 1/2 studies (NCT02407990, NCT04068519, NCT04004221).

Methods:Available baseline tumor tissues from patients (pts) with advanced solid tumors who received TIS were tested with either multiplex-immunohistochemistry (m-IHC) (n=67, Opal automation Multiplex IHC kit) or gene expression profile (n=629, HTG EdgeSeq Precision Immuno-Oncology Panel). High/low cell density/signature scores were defined per median score, respectively. Median overall survival (OS) was estimated by the Kaplan-Meier method and log rank test was used to compare survival curves between pts with different biomarker levels.

Results: Pts with a high CD68 density (CD68Hi) (n=34) had a longer OS compared with pts who had a low CD68 density (n=33), with a median OS of 15.0 vs 10.4 months, p=0.11. A weak association was observed between survival and CD8 cell density. When the two cell types were combined as a composite biomarker, pts with high CD8 (CD8Hi) and CD68Hi showed the longest OS (Table). A consistent finding was confirmed in the gene expression population (Table). Further TME analysis revealed that pts with CD8Hi and CD68Hi signature showed most elevated CD8 T cell cytotoxicity (CD8A, GNLY, GZMA, GZMB), T cell trafficking (CXCL9, CXCL10, CCL4, CCL5), MHCI antigen presentation (TAP1, TAP2, HLA.A/B/C) signatures/genes, and enriched expression of pro-inflammatory macrophage polarization pathway (STAT1, SLAMF7/8, ISG15).

Conclusion: Co-enrichment of CD8 T cells and macrophages were associated with survival benefit and an immune-activated TME in pts with various tumor types treated with TIS. This observation warrants further investigation.

Association between ICs and the clinical efficacy of TIS m-IHC analysis CD8Hi/CD68 Hi (n=24) CD8 Hi/CD68Lo (n=10) CD8 Lo/CD68Hi (n=10) CD8 Lo/CD68Lo (n=23) Median OS, months (95% CI) 15.7 (8.5, NA) 5.1 (0.8, 10.8) 6.3 (1.8, NA) 11.2 (4.0, 17.6) Gene expression analysis CD8Hi/CD68 Hi (n=202) CD8 Hi/CD68Lo (n=113) CD8 Lo/CD68Hi (n=113) CD8 Lo/CD68Lo (n=201) Median OS, months (95% CI) 14.9 (11.2, 19.2) 11.1 (7.1, 13.5) 7.7 (5.6, 11.4) 9.8 (7.4, 11.6) p value* 0.00033 *p value obtained from log-rank test CI, confidence interval; Hi, high density; IC, immune cell; m-IHC, multiplex immunohistochemistry; Lo, low density; NA, not available; OS, overall survival; TIS, tislelizumab

Citation Format: Wei Shen, Tengfei Liu, Yang Shi, Jingwen Shi, Dan Wang, Liang Liang, Silu Yang, Xiaopeng Ma, Wei Jin, Pei Zhang, Ruiqi Huang, Yun Zhang, Zhirong Shen. CD8 T cells and macrophage abundances associated with clinical benefit of tislelizumab in various tumor types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB514.