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 paper evaluated mismatch repair (MMR), programmed death-ligand 1 (PD-L1) and compartment-specific CD3/CD8 tumor-infiltrating lymphocytes (TILs) in resected tumors and explored associations with disease-specific survival (DSS). Ninety-nine patients underwent pancreaticoduodenectomy at Vancouver General Hospital between 1984-2013. Duplicate 0.6-mm tissue microarrays were assessed for MMR proteins, PD-L1 combined positive score (CPS), and stromal and intra-epithelial CD3 and CD8 counts. DSS was estimated by Kaplan-Meier methods. Exploratory Cox models adjusted for age, histologic subtype, pT group, pN status, and adjuvant chemotherapy. There were 44 DSS events. MMR deficiency was present in 37/99 tumors (37.4%). PD-L1 was evaluable in 87 tumors; 57/87 (65.5%) had CPS ≥1 and 24/87 (27.6%) had CPS ≥10. Intraepithelial CD8+ T-cells were present in 23/98 tumors (23.5%). 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 (HR 0.422; 95% 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.