ArticleJournal for immunotherapy of cancer2026
IL-27 shapes NK cell heterogeneity and function in colorectal cancer.
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
backgroundColorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide and is characterized by an immunosuppressive tumor microenvironment (TME). While adaptive immunity contributes to tumor control, growing evidence underscores the role of innate lymphocytes, particularly natural killer (NK) cells, in early antitumor surveillance. However, tumor-infiltrating NK cells often exhibit defective maturation and impaired effector functions, whereas the signals regulating NK cell differentiation and activity in CRC remain poorly defined. Interleukin-27 (IL-27) has emerged as a regulator of antitumor immunity, yet its role in modulating NK cell responses in intestinal tumors is largely unexplored.
methodsWe employed an orthotopic transplantation model of genetically engineered colorectal tumor organoids
resultsSingle-cell transcriptomic profiling revealed marked heterogeneity among tumor-infiltrating NK cells, identifying subsets with different maturation states and functional capacities. Among innate lymphocytes, AKPS tumors were dominated by NK cells displaying reduced activating receptors and diminished cytotoxic and cytokine-producing potential. Phenotypic and adoptive transfer analyses demonstrated that the TME favors persistence of immature CD27
conclusionsOur study identifies IL-27 as a critical modulator of NK cell differentiation and function in CRC, highlighting its role in sustaining NK cell-mediated immune surveillance within the tumor microenvironment. These findings provide mechanistic insight into NK cell dysfunction in CRC and suggest IL-27 signaling as a promising therapeutic target to restore innate antitumor immunity.
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