Our findings identify the PGE2–EP2/EP4 signalling axis as a key mechanism underlying mitochondrial depolarization28,43 and deregulated metabolism of human CD8+ T cells in tumour tissue, and establish a mechanistic link to a defect in the IL-2–mTOR–pS6 pathway underlying inefficient responses by human TILs. Here, PTGER2 is linked to neoplasm.