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

18 March 2026 at 18:00

Clin Cancer Res. 2026 Mar 18. doi: 10.1158/1078-0432.CCR-25-4153. Online ahead of print.

ABSTRACT

PURPOSE: Intestinal 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 DESIGN: This multicenter retrospective and prospective study included mNSCLC patients 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, 1-3 Gy, and >3 Gy groups and treatment outcomes were compared. The blood and fecal samples were subjected to multi-omics profiling.

RESULTS: g>309 patients were included in the retrospective analysis. Optimal efficacy was observed with a small intestinal mean radiation dose (SIMRD) of 1-3 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 1-3 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 1-3 Gy. Responders were enriched in Bacillota, Clostridia, and indole derivatives, particularly indole-3-carboxylic acid. Moreover, the 1-3 Gy group exhibited increased circulating macrophage inflammatory protein-3Ξ± and reduced circulating Ξ±4Ξ²7+ regulatory T cells.

CONCLUSIONS: ILDR influences the efficacy of PD-1 blockade in patients with mNSCLC, particularly when SIMRD is maintained within the 1-3 Gy range, likely through modulation of the gut microbiota-metabolite-immune axis.

PMID:41849236 | DOI:10.1158/1078-0432.CCR-25-4153

CAPT: Confusion-Aware Prompt Tuning for Reducing Vision-Language Misalignment

arXiv:2603.02557v1 Announce Type: cross Abstract: Vision-language models like CLIP have achieved remarkable progress in cross-modal representation learning, yet suffer from systematic misclassifications among visually and semantically similar categories. We observe that such confusion patterns are not random but persistently occur between specific category pairs, revealing the model's intrinsic bias and limited fine-grained discriminative ability. To address this, we propose CAPT, a Confusion-Aware Prompt Tuning framework that enables models to learn from their own misalignment. Specifically, we construct a Confusion Bank to explicitly model stable confusion relationships across categories and misclassified samples. On this basis, we introduce a Semantic Confusion Miner (SEM) to capture global inter-class confusion through semantic difference and commonality prompts, and a Sample Confusion Miner (SAM) to retrieve representative misclassified instances from the bank and capture sample-level cues through a Diff-Manner Adapter that integrates global and local contexts. To further unify confusion information across different granularities, a Multi-Granularity Difference Expert (MGDE) module is designed to jointly leverage semantic- and sample-level experts for more robust confusion-aware reasoning. Extensive experiments on 11 benchmark datasets demonstrate that our method significantly reduces confusion-induced errors while enhancing the discriminability and generalization of both base and novel classes, successfully resolving 50.72 percent of confusable sample pairs. Code will be released at https://github.com/greatest-gourmet/CAPT.
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