Long non-coding RNAs and their potential role in predicting immunotherapy response and prognosis: a systematic review
Abstract
Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, durable clinical benefit is limited to a subset of patients. Long non-coding RNAs (lncRNAs) have emerged as important regulators of tumor biology and immune responses and may serve as novel biomarkers to predict prognosis and response to ICIs.
Methods: The systematic review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251030158). Databases were searched from January 2010 to July 2025 for studies evaluating lncRNA expression in adult cancer patients treated with ICIs. Eligible studies assessed associations between lncRNAs expression and survival outcomes after ICI treatment.
Results: After selection, 31 studies across multiple cancer types, were included. Most studies were retrospective bioinformatic analyses of public datasets and focused on ICI therapies. lncRNA-based signatures consistently demonstrated prognostic value by stratifying patients into groups with significantly different survival outcomes and were associated with variations in ICI response across multiple cancer types.
Conclusions: LncRNAs represent promising prognostic and predictive biomarkers for ICI. Prospective validation and standardized analytical approaches are needed to support their clinical translation in precision immuno-oncology.
Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251030158.
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