ArticleCancer research2025
The Integrated Stress Response Pathway Coordinates Translational Control of Multiple Immune Checkpoints in Lung Cancer.
Article in Cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- Role and clinical significance of VISTA (PD-1H) and PVR (CD155) expression in non-small cell lung carcinoma: a systematic review.Translational lung cancer research · 2026Review
- Monoclonal antibodies targeting PCDH7 inhibit tumor growth and enhance immune responses inScience advances · 2026Article
- The integrated stress response in cancer: mechanisms of tumor adaptation and therapeutic targeting.Biochemical Society transactions · 2026Review
- Targeting the epigenome and the integrated stress response to normalize colorectal cancer subclonal plasticity and progression.Cell death & disease · 2026Article
- Overcoming immunotherapy resistance in breast cancer: a novel strategy by targeting the integrated stress response.Frontiers in cell and developmental biology · 2026Review
- Sensitization strategy for sonodynamic therapy.Theranostics · 2026Review
- Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.Biomarker research · 2025Review
- Reduction-responsive RNAi nanoplatform for enhanced cancer sonoimmunotherapy via dual inhibition of mitophagy and Nrf2 pathways.Theranostics · 2025Article
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18 authors.
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Abstract
The integrated stress response (ISR) is an adaptive pathway hijacked by cancer cells to survive cellular stresses in the tumor microenvironment. ISR activation potently induces PD-L1, leading to suppression of antitumor immunity. In this study, we sought to uncover additional immune checkpoint proteins regulated by the ISR to elucidate mechanisms of tumor immune escape. The ISR coordinately induced cluster of differentiation 155 (CD155) and PD-L1, enhancing translation of both immune checkpoint proteins through bypass of inhibitory upstream open reading frames in their 5' untranslated regions. Analysis of primary human lung tumors identified a significant correlation between expression of PD-L1 and CD155. ISR activation accelerated tumorigenesis and inhibited T-cell function, which could be overcome by combining PD-1 and TIGIT blockade with the ISR inhibitor ISRIB. This study uncovers a mechanism by which two immune checkpoint proteins are coordinately regulated and suggests a therapeutic strategy for patients with lung cancer. SIGNIFICANCE: The integrated stress response represents a targetable axis to improve the efficacy of immunotherapy in lung cancer by inhibiting the coordinated translational regulation of the PD-L1/PD-1 and CD155/TIGIT immune checkpoint pathways.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.