Spatial MSC Index for Predicting Anti-PD-1 Efficacy in Esophageal Cancer

The intratumoral microbiota is a key modulator of the tumor immune microenvironment. This study aims to clinically validate a novel, AI-driven digital pathology biomarker-the Microbial-Sensory Coupling (MSC) index-which measures the spatial proximity between the intratumoral bacterium Campylobacter gracilis(C. gracilis) and host Trace Amine-Associated Receptor 1 (TAAR1)+ tumor cells. The study will evaluate whether the MSC index, measured in pre-treatment tumor biopsy tissues, can accurately predict clinical responsiveness and survival outcomes in ESCC patients undergoing anti-PD-1-based immunotherapy.

Inclusion Criteria: 1. Histologically confirmed esophageal squamous cell carcinoma (ESCC). 2. Received standard anti-PD-1 antibody therapy (e.g., pembrolizumab, camrelizumab, sintilimab, toripalimab) combined with chemotherapy or as monotherapy, with at least one post-treatment response evaluation available. 3. Availability of adequate, high-quality archived pre-treatment tumor tissue biopsies (FFPE blocks or unstained slides) containing sufficient tumor and stromal areas. 4. At least one measurable target lesion according to RECIST 1.1 criteria at baseline. 5. ECOG performance status of 0 or 1 at the initiation of anti-PD-1 therapy. 6. Complete clinicopathological and follow-up data retrievable from medical records. Exclusion Criteria: 1. Histology other than squamous cell carcinoma (e.g., adenocarcinoma, small cell carcinoma). 2. Prior systemic exposure to anti-PD-1, anti-PD-L1, anti-CTLA-4, or other immunotherapy agents. 3. Concomitant systemic antibiotic, antifungal, or antiviral treatment within 14 days prior to tissue biopsy collection. 4. Active autoimmune diseases or psychiatric disorders that prevent compliance. 5. Insufficient tumor tissue specimen for dual ISH-IF spatial analysis.