Systems approaches to characterize the local heterogeneities in NK cell antitumor immunity in MHC I-disparate human non-small cell lung cancer

Abstract Checkpoint immunotherapy has shown encouraging yet limited success in non-small cell lung cancer (NSCLC) patients. We combined multiplexed fluorescence imaging with quantitative spatial analysis to investigate antitumoral immunity NSCLC. As seen before, we observed frequent MHC class I (MHC I) loss and development of CD8 T refractory tumors. I-deficiency suggested NK cells may confer protection Indeed, found higher CD3 −CD56 +NK numbers were associated both disease-free overall survival. Using partial least squares regression, that significantly enriched I-bearing Quantitative characterization tumor expression revealed vast intra- inter-tumoral heterogeneity, which was highly the local lymphocyte landscape. To infer functional differences cell-cell communication, built computational models based on single neighborhood profiles discriminate between IFNg-disparate lymphocytes. IFNg more frequently other or comparison −NK cells, +T had −lymphocyte neighbors. Moreover, unique their capacity also associate −tumor cells. Together these data implicate a key role for recruiting activating lymphocytes tumors, further suggest be developing effective therapies even Supported by UVA Carter Immunology Center Collaborative Research Award