Extended Data Fig. 6: Differential gene expression profiles of CD39⁻ and CD39⁺ CD8⁺ TILs.

a, In order to better characterize CD39⁺ CD8⁺ TIL cells, we sorted and performed transcriptomic profiling on CD39⁻ and CD39⁺ CD8⁺ TILs. Using PCA on the complete transcriptomic data we observed a natural ordering of samples from naive to effector memory PBMCs, then CD39⁻ CD8⁺ TILs, and finally CD39⁺ CD8⁺ TILs along the PC1 axis (See Fig. 4). We then used GSEA to biologically interpret PC1. Among all pathways that were significantly upregulated, we found CD39⁺ CD8⁺ TILs were enriched in pathways related to cell proliferation and the adaptive immune response, which suggests that these cells were subjected to higher TCR signalling (See detailed list on Supplementary Table 5). b, To obtain a more comprehensive overview of the difference between CD39⁻ and CD39⁺ CD8⁺ TILs, we studied gene sets specific for exhaustion, a pathway characteristic of chronically stimulated T cells^28,29. In line with the hypothesis that CD39 marks CD8⁺ TILs for chronic antigen stimulation, the gene set described for exhaustion (c) was significantly enriched in CD39⁺ CD8⁺ TILs in both colorectal and lung cancer (See Fig. 4).