Herein, we began by integrating the coupled scTCRseq/RNAseq Caushi et al. lung cancer and Oliveira et al. melanoma datasets8,9, each with functionally-validated MANA-specific TIL, to develop and validate ‘MANAscore’, a bioinformatic scoring algorithm based on weighted expression of only 3 genes whose expression has previously been shown to mark tumor-reactive TIL: CXCL13, ENTPD1, and IL7R. The MANAscore exhibited superior performance than the aforementioned published signatures in distinguishing MANA-specific TIL from bystander TIL. This evidence concerns the gene ENTPD1 and neoplasm.