biostudies-literatureRodriguez-Garcia GJNIDCR NIH HHSNIDDK NIH HHSNIAID NIH HHSNHLBI NIH HHSNCI NIH HHS464-477https://www.ebi.ac.uk/biostudies/studies/S-EPMC11220743biostudies-literatureUnknown8(6)PD-1 blockade has been approved for head and neck squamous cell carcinoma (HNSCC) patients. However, many HNSCC patients do not respond to this treatment, and other tumor microenvironmental factors may promote resistance to PD-1 blockade. We previously identified increased expression of the inhibitory receptor NKG2A on CD8+ T cells in HNSCC tumors compared with T cells in matching PBMC samples. Mechanisms that promote NKG2A expression and the role of NKG2A on human T cells in the tumor microenvironment, however, are uncertain. In this study, we show that tumor-conditioned media (TCM) of HNSCC cancer cell lines or ascites fluid from colorectal carcinoma patients is sufficient to induce the expression of NKG2A and other inhibitory receptors on activated CD8+ T cells isolated from PBMCs of heImmunoHorizonsCancer Cell Small Molecule Secretome Induces the Immune Checkpoint NKG2A and Dysfunction of Human CD8+ T Cells.PMC11220743R01 DE027749P30 DK058404R01 HL136664R01 CA217987T32 AI138932Rodriguez-Garcia GJGraves DKKim YJIdrees KRathmell JCMirza MBKorrer MJfalseCancer Cell Small Molecule Secretome Induces the Immune Checkpoint NKG2A and Dysfunction of Human CD8+ T Cells.PD-1 blockade has been approved for head and neck squamous cell carcinoma (HNSCC) patients. However, many HNSCC patients do not respond to this treatment, and other tumor microenvironmental factors may promote resistance to PD-1 blockade. We previously identified increased expression of the inhibitory receptor NKG2A on CD8+ T cells in HNSCC tumors compared with T cells in matching PBMC samples. Mechanisms that promote NKG2A expression and the role of NKG2A on human T cells in the tumor microenvironment, however, are uncertain. In this study, we show that tumor-conditioned media (TCM) of HNSCC cancer cell lines or ascites fluid from colorectal carcinoma patients is sufficient to induce the expression of NKG2A and other inhibitory receptors on activated CD8+ T cells isolated from PBMCs of he2024-01-01T00:00:00Z2024 Jun2026-05-29T09:57:02.586Z2025-04-04T12:21:49.319ZS-EPMC112207433892228810.4049/immunohorizons.2400046