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Intra-tumoral CD39+CD8+ T cells predict response to PD-1/PD-L1 blockade in patients with NSCLC

Authors: Yeong, Joe; Suteja, Lisda; Simoni, Yannick; Lau, Kah Weng; Tan, Aaron C.; Li, Hui Hua; Lim, Sherlly; Loh, Jie Hua; Yu Ting, Felicia Wee; Nerurkar, Sanjna Nilesh; Takano, Angela; Tan, Eng Huat; Hon Lim, Tony Kiat; Newell, Evan W.; Tan, Daniel S. W.

Online: https://www.sciencedirect.com/science/article/pii/S1556086421021559

Issue:  J Thorac Oncol. 2021 Aug;16(8):1349-1358.


Programmed cell death-1 (PD-1)/ programmed death-ligand 1 (PD-L1) blockade is currently widely used in the treatment of metastatic non-small cell lung cancer (NSCLC). Despite available biomarker stratification, clinical responses vary. Thus, the search for novel biomarkers with improved response prediction is ongoing. Previously, using mass cytometry deep immune-profiling (CyTOF), our group provided evidence that CD39+CD8+ T cells represent tumor antigen-specific, cytotoxic T cells in treatment-naïve NSCLC. We hypothesized that accurate quantitation of this T cell subset would predict immunotherapy outcome. Methods In order to translate this to a clinical setting, the present study compared CyTOF data to results obtained via a range of clinically relevant methods; including conventional immunohistochemistry (IHC), multiplex immunohistochemistry/immunofluorescence (mIHC/IF), and gene expression assay by NanoString. Results Quantification using mIHC/IF but not conventional IHC or NanoString correlated with the CyTOF results. The specificity and sensitivity of mIHC/IF was then assessed in a separate retrospective NSCLC cohort. CD39+CD8+ T cell proportion, as determined by mIHC/IF, successfully stratified responders and non-responders to PD-1/PD-L1 inhibitors (Objective Response Rate 63.6%, compared to 0% for the negative group). This predictive capability was independent from other confounding factors, such as total CD8+ T cell proportion, CD39+ lymphocyte proportion, PD-L1 positivity, epidermal growth factor receptor mutation status, and other clinicopathological parameters. Conclusion Our results suggest that the mIHC/IF platform is a clinically relevant method to assess CD39+CD8+ T cell proportion and this marker can serve as a potential biomarker that predicts response to PD-1/PD-L1 blockade in NSCLC patients. Further validation in additional NSCLC cohorts is warranted.