Figure 4 from Cytotoxic NK Cells Impede Response to Checkpoint Immunotherapy in Melanoma with an Immune-Excluded Phenotype

Pharmacologic targeting of NK cells. A, Uniform Manifold Approximation and Projection (UMAP) of re-clustered NK cells from the NRAS;Ink4a and YUMM5.2 tumors (left), selected genes expression between NK cell clusters (middle), and proportions of NK cells from the NRAS;Ink4a and YUMM5.2 tumors compared between control- and αPD-1–treated condition (right) based on the scRNA-seq experiment. B, Dot plot of the expression of selected genes between NRAS;Ink4a and YUMM5.2 tumors in NK cells only based on the scRNA-seq experiment. C, Volcano plot representing differentially expressed proteins in NK cells from the NRAS;Ink4a tumor between control and αPD-1 treatment. Significantly expressed proteins were considered based on the adjusted P value > 10e–3 based on the CITE-seq experiment. D, Growth curves (left) and doubling time calculation (right) of NRAS;Ink4a tumors in vivo treated with αPD-1, JMS-17-2, and CD38 (n ≥ 4 per cohort and a Welch-corrected t test was performed on the doubling time of tumors upon exponential fitting; **, P < 0.01). E, Quantification of immune cells (CD45⁺), NK cells (CD45⁺NKP46⁺), CD8⁺ T cells (CD45⁺CD3ε⁺CD8α⁺), and macrophages (CD45⁺F4/80⁺) in multiplexed immunofluorescence images (each dot corresponds to a single tumor; data analyzed with a Welch-corrected t test; *, P < 0.05; **, P < 0.01). Tumor rim corresponds to an area ≤0.2 mm² in proximity to the tumor border.