Glutamine promotes human CD8

T cells protect tissues from cancer. Although investigations in mice showed that amino acids (AA) critically regulate T cell immunity, this remains poorly understood in humans. Here, we describe the AA composition of interstitial fluids in keratinocyte-derived skin cancers (KDSCs) and study the effect of AA on T cells using models of primary human cells and tissues. Gln contributed to - 15% of interstitial AAs and promoted interferon gamma (IFN- g ), but not granzyme B (GzB) expression, in CD8 + T cells. Furthermore, the Toll -like receptor 7 agonist imiquimod (IMQ), a common treatment for KDSCs, down -regulated the metabolic gatekeepers c-MYC and mTORC1, as well as the AA transporter ASCT2 and intracellular Gln, Asn, Ala, and Asp in T cells. Reduced proliferation and IFN- g expression, yet increased GzB, paralleled IMQ effects on AA. Finally, Gln was sufficient to promote IFN- g- production in IMQ-treated T cells. Our findings indicate that Gln metabolism can be harnessed for treating KDSCs.