Fig. 2: Anti-MAA T cells are exhausted but retain stem-like properties and form the most inhibitory interactions with Treg and tumor cells.
From: Evolution and modulation of antigen-specific T cell responses in melanoma patients
a UMAP projection of expression profiles of tumor-infiltrating lymphocytes (TIL) from 25 treatment naïve or immunotherapy resistant metastatic melanoma patients, colored by cluster. (Data from ref. 30). b The same UMAP projection as in panel A where the TCRGP-predicted anti-MAA and anti-viral T cells are highlighted. Melanoma-specific clonotypes include T cells that were predicted by their TCRs to be reactive against epitopes from melanoma-associated antigens MART1AAGIGILTV, MART1ELAGIGILTV, MELOE1TLNDECWPA, TKTAMFWSVPTV, and SEC24AFLYNLLTRV. Encircled lines denote enrichment (Padj < 0.05, Benjamini–Hochberg corrected one-sided Fisher’s exact test) to the clusters shown in panel A. (Data from ref. 30). c Bar plot showing the enrichment of anti-MAA and anti-viral clonotypes to different T cell phenotypes as P-values from Fisher’s one-sided exact test. (Data from ref. 30). d The differentially expressed genes (Padj < 0.05, Bonferroni corrected two-sided t-test) between anti-MAA and anti-viral clonotypes in patients with melanoma. (Data from ref. 30). e Bar plot showing the log2 fold-change of the number of statistically significant (P < 0.05, two-sided permutation test from CellPhoneDB) ligand–receptor interactions between anti-MAA or anti-viral clonotypes and the cell types found in the tumor microenvironment as predicted by CellPhoneDB permutation test. (Data from ref. 30). f The statistically significant (P < 0.05, two-sided permutation test from CellPhoneDB) inhibitory ligand-receptor pairs between anti-MAA clonotypes and cells in the tumor microenvironment of melanoma. (Data from ref. 30). g UMAP projection of expression profiles of TILs from patients with primary or metastatic uveal melanoma (n = 9), colored by cluster. (Data from ref. 34). h Focused UMAP of T cells with recovered TCRs from panel (g). On the top row, the clustering is colored by T cell phenotypes and the TCRGP-predicted anti-MAA and anti-viral clonotypes are shown. The dashed circles denote enrichment (Padj < 0.05, Benjamini–Hochberg corrected one-sided Fisher’s exact test) to clusters shown in panel h. A selection of the expression of canonical markers used to define the clusters are highlighted. (Data from ref. 34). i The differentially expressed genes (Padj < 0.05, Bonferroni corrected two-sided t-test) between anti-MAA and anti-viral clonotypes in patients with uveal melanoma. (Data from ref. 34). j The statistically significant (P < 0.05, two-sided permutation test from CellPhoneDB) inhibitory ligand-receptor pairs between anti-MAA clonotypes and cells in the tumor microenvironment of uveal melanoma (Data from ref. 34). Source data are provided as a Source Data file.
