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Review 2026

Non-coding RNAs related to PD1/PD-L1 signaling with potential diagnostic, prognostic, and therapeutic value in the tumorigenesis of brain cancers

Brain cancers are among the most aggressive malignancies associated with significant global morbidity and mortality. Cancer immunotherapy has emerged as a promising novel approach for the treatment of brain cancer through regulating the PD-1/PD-L1 signaling and disrupting tumor immune escape. Several targeted therapies have been developed to inhibit the PD-1/PD‑L1 route, but reduced therapeutic responses and drug resistance remain a major challenge that needs to be addressed. Notably, non-coding RNAs (ncRNAs), which include microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), exert crucial effects on cell proliferation, invasion, and immune escape in the tumor microenvironment (TME). It has been shown that ncRNAs reduce tumor formation and progression by regulating the PD-1/PD-L1 pathway and by down-regulating key transcription factors, including NF-κB, JAK, and STAT. Therefore, identifying novel regulatory ncRNAs and their associated target genes offers promising opportunities for developing therapeutic interventions against brain cancer. This review highlights recent advances in understanding the regulatory role of ncRNAs on the PD-1/ PD-L1 pathway in brain cancer tumorigenesis.

Reihane Behnam-Rassouli, Farzaneh Entezari, Majid Ghorbanzadeh et al. · 0 citations
Review Aug 2026

Mechanisms of Resistance to Immune Checkpoint Inhibitors and Therapeutic Strategies to Overcome Them: An Integrative Review.

Immune checkpoint inhibitors (ICIs) targeting PD-1, PD-L1, CTLA-4, and LAG-3 have transformed cancer therapy, but resistance limits durable benefit. This integrative review summarizes primary, adaptive, and acquired resistance driven by tumor-intrinsic defects, suppressive tumor microenvironmental programs, and host-related factors. We discuss mechanism-based strategies to overcome resistance, including combination immunotherapy, antiangiogenic treatment, TGF-β targeting, myeloid reprogramming, epigenetic and metabolic interventions, microbiome modulation, and cellular or vaccine-based approaches. The findings support a precision immuno-oncology framework based on composite biomarkers, longitudinal monitoring, and adaptive treatment selection matched to dominant resistance mechanisms.

Ehsan Lotfi, F. Golab · 0 citations

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