LAG3 and neoplasm: Among the co-stimulatory molecules, upregulation of CD27, which participates in the generation of memory CD8+ T cells (42), was observed in all CD4+ T cell clusters except for the CD4-C4-Treg-FOXP3 cluster; TNFRSF14, which enhances the tumor-specific immune response (45), increased in all CD4+ T cell clusters except for the CD4-C2-naive-LEF1 cluster; and LAG3, a marker of exhaustion (46), showed no significant change in CD4+ T cell clusters (Supplementary Figures S5B–E).