The most differentially upregulated genes in anti-melanoma clonotypes included genes associated with activated, cytotoxic functions in CD8+ T cells (e.g., NKG7, GZMA, GZMK), different cytokines (CCL4, CCL5), T cell activation (CD74, HLA-DRA), and inhibitory markers such as HAVCR2 (TIM3), arguing further for their role as tumor-reactive cells (Fig. 2d and Supplementary Data 3). This evidence concerns the gene CD8A and neoplasm.