ArticleJournal for immunotherapy of cancer2026
NKG2A-HLA-E axis contributes to an immunosuppressive checkpoint network in hepatocellular carcinoma.
Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThe immunosuppressive tumor microenvironment in hepatocellular carcinoma (HCC) limits the efficacy of current immunotherapies. The interplay between the emerging inhibitory receptor NKG2A and its activating counterpart NKG2C, both binding HLA-E, and its interaction with the PD-1-PD-L1 pathway in cancer remains unclear. This study aims to delineate the functional network formed by these pathways in shaping the immunosuppressive landscape of HCC.
methodsWe analyzed public databases and performed immunohistochemistry on HCC tissues to assess HLA-E expression and prognostic relevance. Tumor-infiltrating lymphocytes from patient samples were examined by flow cytometry to evaluate the functional impact of NKG2A, NKG2C, and PD-1 expression on T and NK cells. Single-cell RNA and T cell receptor (TCR) sequencing were employed to characterize immune subset heterogeneity. Functional assays and mouse models were used to evaluate the effects of NKG2A and PD-1 blockade.
resultsIn the absence of CD8
conclusionsOur findings identify the NKG2A-HLA-E axis as an important immunoregulatory pathway associated with immune suppression in HCC and provide a rationale for further evaluation of combined NKG2A and PD-1 blockade strategies.
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