Journal
JOURNAL FOR IMMUNOTHERAPY OF CANCER
Volume 10, Issue 6, Pages -Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/jitc-2021-004440
Keywords
immunotherapy; lymphocytes; tumor-infiltrating; lung neoplasms; tumor biomarkers; programmed cell death 1 receptor
Categories
Funding
- Stand Up To Cancer - American Cancer Society Lung Cancer Dream Team Translational Research Grant [SU2C-AACR-DT1715]
- NIH [R03CA219603, R37CA245154, R01CA262377]
- Mark Foundation EXTOL project [19-029-MIA]
Ask authors/readers for more resources
Baseline T cell density and exhaustion marker expression can stratify outcomes in PD-L1 positive patients with NSCLC treated with ICI. Spatial immune heterogeneity can be measured using the RQI and is associated with survival in NSCLC.
Background Tumor infiltrating lymphocytes (TILs) reflect adaptive antitumor immune responses in cancer and are generally associated with favorable prognosis. However, the relationships between TILs subsets and their spatial arrangement with clinical benefit from immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC) remains less explored. Methods We used multiplexed quantitative immunofluorescence panels to determine the association of major TILs subpopulations, CD8(+) cytotoxic T cells, CD4(+) helper T cells and CD20(+) B cells, and T cell exhaustion markers, programmed cell death protein-1 (PD-1),lymphocyte-activation gene 3 (LAG-3) and T cell immunoglobulin mucin-3 (TIM-3) with outcomes in a multi-institutional cohort of baseline tumor samples from 179 patients with NSCLC treated with ICI. The analysis of full-face tumor biopsies including numerous fields of view allowed a detailed spatial analysis and assessment of tumor immune heterogeneity using a multiparametric quadratic entropy metric (Rao's Q Index (RQI)). Results TILs were preferentially located in the stromal tissue areas surrounding tumor-cell nests and CD8(+) T cells were the most abundant subset. Higher density of stromal CD8(+) cytotoxic T cells was significantly associated with longer survival, and this effect was more prominent in programmed death ligand-1 (PD-L1) positive cases. The role of baseline T cell infiltration to stratify PD-L1 expressing cases was confirmed measuring the T cell receptor-burden in an independent NSCLC cohort studied with whole-exome DNA sequencing. High levels of LAG-3 on T cells or elevated RQI heterogeneity index were associated with worse survival in the cohort. Conclusion Baseline T cell density and T cell exhaustion marker expression can stratify outcomes in PD-L1 positive patients with NSCLC treated with ICI. Spatial immune heterogeneity can be measured using the RQI and is associated with survival in NSCLC.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available