High density of TCF1+ stem-like tumor-infiltrating lymphocytes is associated with favorable disease-specific survival in NSCLC.

Introduction: Tumor-infiltrating lymphocytes are both prognostic and predictive biomarkers for immunotherapy response. However, less is known about the survival benefits oftheir subpopulations.

Methods: Using machine learning models, we assessed the clinical association of the CD8+, PD1+, TCF1+ cel l subset by multiplex immunohistochemistry using tissue microarrays in 553 non-small cell lung cancer (NSCLC) patients and its correlation with other immune cell biomarkers.

Results: We observed positive correlations between TCF1 and CD20 (r=0.37), CD3 (r=0.45)and CD4 (r=0.33). Notably, triple positive (CD8+PD1+TCF1+) were rare, only observed in 29 of 553 patients (5%). Our analysis revealed that cells coexpressing TCF1 with either CD8+ or PD1+ were independent prognostic markers of disease-specific survival in multivariable analysis (HR=0.728, p=0.029 for CD8+TCF1+, and HR=0.612, p=0.002 for PD1+TCF1+). To pilot the subtype of abundant CD8-TCF1+ cells, we explored an immune cell infiltrated whole slideimage and found the majority to be CD4+.

Discussion: Overall, these findings suggest that assessment of CD8+, PD1+, TCF1+ could serve as a potential prognostic biomarker in NSCLC.