What question did this study set out to answer?

This study aims to investigate the impact of low-dose intestinal irradiation on the efficacy of PD-1 blockade in metastatic non-small cell lung cancer patients.

May 29, 2026

Low-dose intestinal irradiation to enhance the efficacy and prognosis of PD-1 blockade in metastatic non-small cell lung cancer.

Key Points

This study aims to investigate the impact of low-dose intestinal irradiation on the efficacy of PD-1 blockade in metastatic non-small cell lung cancer patients.
Multicenter prospective and retrospective study with 301 patients receiving PD-1 inhibitors and abdominopelvic radiotherapy.
Patients stratified by intestinal radiation doses: <1 Gy, 1–3 Gy, and >3 Gy.
Multi-omics analyses conducted on blood and fecal samples from participants.
Patients with 1–3 Gy radiation achieved a 48.8% response rate and median overall survival of 23.7 months (P < 0.01).
SIMRD >3 Gy and <1 Gy were negatively associated with overall survival (HR = 4.96, P < 0.001; HR = 1.90, P < 0.001).
Responders had enriched Bacillota and Clostridia, and higher macrophage inflammatory protein-3α levels.

Abstract

2627 Background: Intestinal low-dose irradiation (ILDR) has been shown to enhance the efficacy of immunotherapy in advanced solid tumors by modulating the gut microbiota and metabolism. However, its role in metastatic non-small cell lung cancer (mNSCLC), particularly in the first-line treatment setting, remains unclear. Therefore, this study investigated the impact of intestinal radiation dose on the efficacy and prognosis of programmed cell death protein 1 (PD-1) blockade in patients with mNSCLC. Methods: This multicenter retrospective and prospective study included patients with mNSCLC who received first- or second-line PD-1 inhibitors combined with abdominopelvic radiotherapy between 2018 and 2025. Patients were stratified into three groups according to the mean intestinal radiation dose: 3 Gy, and treatment outcomes were compared among groups. In addition, blood and fecal samples prospectively collected were subjected to multi-omics analyses. Results: A total of 301 patients were included in the retrospective analysis, among whom 105 patients (34.9%) had a small intestinal mean radiation dose (SIMRD) 3 Gy groups, the 1–3 Gy group also demonstrated significantly prolonged progression-free survival (PFS, 10.2 months) and overall survival (OS, 23.7 months) (P 3 Gy (HR = 4.96, P 3 Gy: 90.0% vs. 63.7% vs. 33.3%; P = 0.041) and the longest median PFS (1-3 Gy vs. 3 Gy: not reached vs. 9.3 months vs. 5.8 months; P = 0.120). Multi-omics analyses revealed that responders were enriched in Bacillota , Clostridia , and indole-derived metabolites, particularly indole-3-carboxylic acid. Moreover, patients in the 1–3 Gy group exhibited increased circulating macrophage inflammatory protein-3α levels and a reduced proportion of α4β7 + regulatory T cells. Conclusions: ILDR influences the efficacy of PD-1 inhibitor therapy in patients with mNSCLC, with the most pronounced benefit observed when SIMRD is maintained within the 1–3 Gy range. This effect may be mediated through modulation of the gut microbiota–metabolite–immune axis.

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