Fig. 4

Shared transcriptional signature of inflammatory Th1 and Th17 cells and exhausted T cells. Pathogenic Th17 cells are established drivers of multiple autoimmune diseases. Exhausted T cells are hypo-functional T cells preventing active tumor immunity. Both T-cell states share part of their transcriptional signature. Interestingly, when projecting the cancer exhaustion signature²⁴⁹ and the pathogenic Th17 signature²³⁹ on the tSNE plot of single-cell CD8⁺ TILs (top), multiple single cells show enrichment for both signatures, suggesting that shared modules or transcriptional programs are activated in those cells. Members of this shared signature could play a key role in T-cell activation and later exhaustion. Targeting of these genes could potentially yield in an enhanced anti-tumor immunity without increased autoimmunity