Immunological profiling of tumor-infiltrating CD8+ T lymphocytes in primary non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), breast cancer (BCa), and renal cell cancers (RCC).
AAI Annual Meeting; May 6-10; Portland, OR. 2022
oregon; portland; chiles
To explore whether the variation in clinical response to immune checkpoint blockade (ICB) reflects intrinsic characteristics of tumor-infiltrating lymphocytes (TIL), TILs from multiple tumor types were analyzed by multiparameter flow cytometry. Recent work identified CD39+CD103+ double positive (DP) CD8 TIL as tumor-reactive, therefore we assessed this phenotype in primary NSCLC (n=28), BCa (n=23), HNSCC (n=23), and RCC (n=23) specimens. TILs from NSCLC and HNSCC had significantly higher frequencies of DP T cells than BCa and RCC (NSCLC: median=34.2, IQR=15.0-53.8%; HNSCC: median=28.6%, IQR=13.5-44.5%), while TILs from BCa and RCC had low frequencies of DP T cells (BCa: median=2.4%, IQR=1.1-3.9%; RCC: median=4.2%, IQR=1.5-16.6%). Additionally, DP cells in NSCLC and HNSCC were co-expressed immune checkpoint markers PD-1, TIM-3, and LAG-3 at a higher frequency than RCC or BCa (P<0.05). DP CD8 T cells in NSCLC and HNSCC also exhibited increased effector potential (granzyme B+) as compared to BCa and RCC, suggesting functional differences. Expression of the transcription factor Eomesodermin, associated with T cell exhaustion, was higher in effector CD8 T cells from RCC (median=84.5%, IQR=44.9-97.4%) as compared to NSCLC (median=28.7%, IQR=20.7-61.4%), BCa (median=30.1%, IQR=0-50%), and HNSCC (median=40.3%, IQR=20.1-61.2%). Additionally, 4-1BB, an indicator of TCR engagement, trended higher in RCC (mean=8.6%, IQR=1.4-46.7%) as compared to BCa (median=1.9%, IQR=0.4-8.6%). These data highlight the heterogeneity of human TILs isolated from distinct tumor types and provide insight into the basal expression of actionable therapeutic targets.
Earle A. Chiles Research Institute
Miller, W; Redmond, William L.; and See full list of authors in comments, "Immunological profiling of tumor-infiltrating CD8+ T lymphocytes in primary non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), breast cancer (BCa), and renal cell cancers (RCC)." (2022). Articles, Abstracts, and Reports. 6122.