ArticleJournal for immunotherapy of cancer2026
PRKX-mediated stabilization of PD-L1 characterizes an immunosuppressive gastric cancer subtype.
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
backgroundGastric cancer (GC) derives limited benefit from immunotherapy, with clinical responses observed in only a minority of patients. Increasing evidence suggests that heterogeneity within the tumor immune microenvironment (TME) is a critical determinant of immunotherapeutic efficacy, highlighting the need for precise immune stratification and the identification of molecular biomarkers that shape the TME.
methodsWe integrated single-cell transcriptomic data from our cohort and public datasets to characterize immune microenvironment heterogeneity in GC. Functional experiments were performed using in vitro assays and in vivo mouse models to investigate the molecular mechanisms regulating immune exhaustion. Clinical relevance was evaluated using tumor specimens from patients with GC receiving anti-programmed cell death protein 1 (PD-1) therapy. Survival analyses and biomarker evaluation were conducted to assess the prognostic and predictive value of candidate markers.
resultsWe identified two distinct GC immune microenvironment subtypes: the immunosuppressive (GC1) and the immune-activated (GC2). PRKX was identified as a key regulator associated with immune heterogeneity and exhaustion. Clinically, a high density of PanCK
conclusionPRKX drives immune exhaustion in the GC1 subtype by stabilizing PD-L1 through phosphorylation-dependent inhibition of ubiquitination, thereby promoting immune evasion. Targeting PRKX represents a potential strategy to overcome resistance to anti-PD-1 therapy, and PRKX expression may serve as a prognostic biomarker to guide immunotherapy in GC.
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