Single-cell profiling reveals the heterogeneity of NK cells during anti-PD-1 therapy in non-small-cell lung cancer

Background: The efficacy of immune checkpoint inhibitors remains limited in non-small cell lung cancer (NSCLC). Natural killer (NK) cells serve as the key element of innate immunity and play an important role in anti-tumor immunity, the impact of NK cells on efficacy of anti-PD-1 therapy in NSCLC is worth exploring.Methods: We analyzed single-cell transcriptome data derived from biopsies of NSCLC patients receiving anti-PD-1 treatment. Immune cell subtypes were identified and further cell-cell communication were analyzed and verified.Results: We observed totally 6 distinct NK cells clusters in NSCLC infiltrating immune cells. It's worth noting that enrichment of immature NK cells was found in responsive group. A series of marker genes of immature NK cells were associated with anti-PD-1 response and related to immune regulation processes such as antigen processing, Th1, Th17 cells activation. Moreover, effector CD8+ T cells were significantly enriched in responsive group and showed similar trajectories with immature NK cells. Cell-cell communication analysis showed that immature NK cells showed strong interactions with Th17 cells and effector CD8+ T cells. Furthermore, when validating the expression of immature NK cells marker genes, we found that CXCR4 was associated with enriched infiltration of CD8+ T cells.Conclusions: In conclusion, immature NK cells may facilitate the efficacy of anti-PD-1 therapy by interacting with Th1 cells, Th17 cells and enhancing infiltration of effector CD8+ T cells. Our data suggested that NK cells could be a promising target to improve the prognosis of NSCLC patients.

Automated summary

In this study, we analyzed single-cell transcriptome data from NSCLC patients receiving anti-PD-1 treatment. We identified 6 distinct clusters of NK cells in the infiltrating immune cells of NSCLC. It was found that the responsive group had an enrichment of immature NK cells. Marker genes of immature NK cells were associated with anti-PD-1 response and immune regulation processes. Additionally, effector CD8+ T cells were significantly enriched in the responsive group and showed interactions with immature NK cells. The expression of CXCR4 was associated with infiltration of CD8+ T cells.