Density of immunogenic antigens does not explain the presence or absence of the T-cell–inflamed tumor microenvironment in melanoma

Significance The T-cell–inflamed tumor microenvironment correlates with efficacy of immunotherapy. It is critical to understand whether non–T-cell–inflamed tumors lack antigens for T-cell recognition. In melanoma, no difference between inflamed and noninflamed tumors for multiple antigen classes was observed. Synthesized peptides corresponding to predicted HLA-A2 binding epitopes showed no differences between inflamed and noninflamed tumors. Extrapolation of a T-cell signature across The Cancer Genome Atlas showed no correlation between gene expression and mutational burden in any cancer type. These results indicate that lack of spontaneous immune infiltration in solid tumors is unlikely to be due to lack of antigens. Rather, transcriptional profiling suggests lack of Batf3-lineage dendritic cells. Our data suggest that strategies to restore T-cell entry into noninflamed tumors should be developed.