Compartment-Specific CD8 Infiltration and Disease-Specific Survival in Resected Ampullary Adenocarcinoma

Ampullary adenocarcinoma is rare, and its immune biomarker landscape is incompletely characterized. This article evaluated mismatch repair (MMR), programmed cell death ligand 1 (PD-L1; CD274), and compartment-specific CD3 (CD3E)/CD8 (CD8A) tumor-infiltrating lymphocytes (TIL) in resected tumors and explored associations with disease-specific survival (DSS). Ninety-nine patients underwent pancreaticoduodenectomy at Vancouver General Hospital (VGH) between 1984 and 2013. Duplicate 0.6-mm tissue microarrays (TMA) were assessed for MMR proteins, PD-L1 combined positive score (CPS), and stromal and intraepithelial CD3 and CD8 counts. DSS was estimated using the Kaplan-Meier method. Exploratory Cox models were adjusted for age, histologic subtype, pathologic tumor (pT) group, pathologic node (pN) status, and adjuvant chemotherapy. There were 44 DSS events. MMR deficiency (dMMR) was present in 37 of 99 (37.4%) tumors. PD-L1 was evaluable in 87 tumors; 57 of 87 (65.5%) tumors had CPS ≥1, and 24 of 87 (27.6%) tumors had CPS ≥10. Intraepithelial CD8+ T cells were present in 23 of 98 (23.5%) tumors. PD-L1 CPS ≥1, PD-L1 CPS ≥10, and MMR status were not associated with DSS by log-rank testing (P = 0.35, P = 0.98, and P = 0.74, respectively). In the pT-adjusted model, intraepithelial CD8 presence was associated with lower disease-specific hazard [hazard ratio (HR), 0.422; 95% confidence interval (CI), 0.144-0.994; likelihood-ratio P = 0.048], although the Wald sensitivity test was not significant (P = 0.074). Continuous log-transformed intraepithelial CD8 counts showed a concordant, method-dependent signal. dMMR and PD-L1 expression were common in this historical resected cohort. Intraepithelial CD8 infiltration was associated with DSS, but the borderline and inferential method-dependent estimates require external validation. These prognostic data do not establish benefit from immune checkpoint blockade.

Ampullary cancer is a rare disease in which treatment is extrapolated from other gastrointestinal cancers. In this cohort, immune features varied among tumors with functioning MMR. CD8+ T cells within the tumor epithelium showed an exploratory association with improved DSS, which supports the prospective evaluation of immune stratification, not immediate treatment selection.