Elderly Lung Cancer Patients show Tumor-Infiltrating CD8+ T Cell Responses Enriched with PDCD1 and CXCL13 after Neoadjuvant Therapy with Anti-PD-1
DOI:
https://doi.org/10.37155/2972-4759-2023-01-01-3Keywords:
Lung cancer, Aging, Immunosenescence, Neoadjuvant Immunotherapy, anti-PD-1Abstract
Aged individuals are significantly underrepresented in immunotherapy clinical trials for cancer. Little is known regarding the mechanisms that might regulate their responsiveness to immune checkpoint inhibitors (ICIs). Here, we performed a single-cell analysis on public data of tumor-infiltrating lymphocytes (TILs) in 419,107 cells of 11 elderly and 5 non-elderly non-small cell lung cancer (NSCLC) patients treated with neoadjuvant anti-PD-1, comparing gene expression and molecular patterns associated with positive outcomes and tumor clearance. By reprocessing the dataset of an original study focused on characterizing mutation-associated neoantigen infiltrating T cells in lung cancer patients treated with neoadjuvant immunotherapy, we found that, in a comparison between elderly and non-elderly patients, ICI responsiveness is achieved despite age. T cell immunosenescence can be observed both in aged (≥ 65 years) and younger NSCLC individuals. Both elderly and young individuals produced responses with a heterogeneous molecular program associated with tumor-reactive CD8+ TILs. Specifically, T cells from elderly patients showed an enhanced expression of PDCD1 and CXCL13 (p<0.001) in comparison to younger subjects. Altogether, our findings demonstrate favorable molecular signatures in aged NSCLC individuals following anti-PD-1 treatment and suggest that the recruitment of older adults in immunotherapy clinical trials should not be dismissed solely on the grounds of age.
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Copyright (c) 2023 Fernanda Tereza Bovi Frozza, Gabriel F. Pozo de Mattos P., Cristina Bonorino
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