Immunoregulatory NK cells in non small cell lung cancer (NSCLC) 3221

Abstract Description Despite significant advancements in targeted therapies and immunotherapies, a substantial proportion of non-small cell lung cancer (NSCLC) patients remain unresponsive to treatment. One contributing factor is tumor-induced immunosuppression, which impairs effective T cell responses. Natural killer (NK) cells, while playing a pivotal role in antitumor immunity, have been shown to negatively regulate adaptive immune responses in various contexts. In this study, we characterized the phenotype of NK cells within the NSCLC microenvironment and investigated their potential contribution to immune suppression. CD3- CD56+ NK cells were isolated from tumor resection specimens and profiled using single-cell RNA sequencing and CITE-seq. Identified NK cell clusters were subsequently quantified in tumor-infiltrating lymphocyte (TIL) cultures exhibiting different expansion rates. Our analyses identified a tumor-specific NK cell subset associated with reduced recurrence-free survival (RFS). This subset was preferentially enriched in TIL cultures with low expansion rates compared to those with high expansion rates, suggesting a potential role in limiting T cell proliferation. Future investigations will focus on confirming the regulatory role of this NK cell subset and elucidating the mechanisms underlying its suppressive function. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)