ArticleClinical cancer research : an official journal of the American Association for Cancer Research2026
Low-Dose Intestinal Irradiation Enhances the Efficacy and Prognosis of PD-1 Blockade in Metastatic Non-Small Cell Lung Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Harnessing Gut Microbiota to Enhance Immunotherapy in NSCLC: From Mechanisms to Translational Applications.Cancer medicine · 2026Review
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16 authors.
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Abstract
purposeIntestinal low-dose irradiation (ILDR) may enhance immunotherapy efficacy by modulating the gut microbiota and metabolism; however, its role in metastatic non-small cell lung cancer (mNSCLC), particularly in the first-line setting, remains unclear. EXPERIMENTAL
designThis multicenter retrospective and prospective study included patients with mNSCLC receiving first- and second-line programmed cell death protein 1 (PD-1) inhibitors along with abdominopelvic radiotherapy between 2018 and 2025. Patients were stratified by the mean intestinal radiation dose into <1 Gy, 1 to 3 Gy, and >3 Gy groups, and treatment outcomes were compared. The blood and fecal samples were subjected to multiomics profiling.
resultsA total of 309 patients were included in the retrospective analysis. Optimal efficacy was observed with a small intestinal mean radiation dose (SIMRD) of 1 to 3 Gy, showing longer progression-free survival (PFS, 10.2 months) and overall survival (OS, 22.8 months; P < 0.01), which was consistent across subgroups. Compared with 1 to 3 Gy, SIMRD >3 Gy [hazard ratio (HR) = 4.87; P < 0.001] and <1 Gy (HR = 1.85; P < 0.001) independently predicted worse OS. Prospective results confirmed the best disease control rate (P = 0.041) and PFS (P = 0.046) with SIMRD of 1 to 3 Gy. Responders were enriched in Bacillota, Clostridia, and indole derivatives, particularly indole-3-carboxylic acid. Moreover, the 1 to 3 Gy group exhibited increased circulating macrophage inflammatory protein-3α and reduced circulating α4β7+ regulatory T cells.
conclusionsILDR influences the efficacy of PD-1 blockade in patients with mNSCLC, particularly when SIMRD is maintained within the 1 to 3 Gy range, likely through modulation of the gut microbiota-metabolite-immune axis. See related commentary by Deutsch et al., p. 3420.
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