Research ArticlesImmune Microenvironment in Gallbladder AdenocarcinomasPatil, Pallavi A. MD*,†; Lombardo, Kara BSc‡; Cao, Weibiao MD§Author Information Departments of *Pathology §Pathology and Medicine, Rhode Island Hospital and The Alpert Medical School of Brown University, Providence, RI †USA Health University Hospital, Mobile, AL ‡Department of Pathology, the Johns Hopkins Hospital, Baltimore, MD The authors declare no conflict of interest. Reprints: Weibiao Cao, MD, Department of Pathology and Medicine, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, 593 Eddy Street, APC12, Providence, RI 02903 (e-mail: [email protected]). Applied Immunohistochemistry & Molecular Morphology: September 2021 - Volume 29 - Issue 8 - p 557-563 doi: 10.1097/PAI.0000000000000922 Buy Metrics Abstract Programmed death-1 (PD1) expression has not been reported in gallbladder adenocarcinoma. In this study we examined PD1 expression in gallbladder cancer to explore the correlation between PD1 expression and the clinicopathologic parameters. We found that 98% (46/47) cases expressed programmed death-ligand 1 (PD-L1) with 85% cases being PD-L1 3+. PD1+ tumor-infiltrating lymphocytes (TILs) were present in 78.7% cases (37/47). The tumor size was significantly smaller and the stromal CD3+ TILs were significantly higher in tumors with PD1+ TILs than those with PD1− TILs. In the tumors with size of <3 cm, stromal CD3+ TILs >115/HPF or stromal CD8+ TILs >45/HPF were associated with much better survival than those with stromal CD3+ TILs ≤115/HPF or stromal CD8+ TILs ≤45/HPF. In tumors with the size of 3 cm or larger, PD1+ TILs or stromal CD8+ TILs >45/HPF carried a significantly poorer survival than PD1− tumors or stromal CD8+ TILs <=45/HPF. No correlation was identified between PD1 expression and lymphovascular invasion, distant metastasis, pathologic tumor stage or prognostic stage. Multivariate survival analysis showed that tumor TNM stage and age were independent prognostic factors in gallbladder adenocarcinomas. We conclude that gallbladder adenocarcinomas may have high PD-L1 expression and PD1+ TILs. Smaller tumor size and greater amount of stromal CD3+ T cells were found in tumors with PD1+ TILs. In small tumors (<3 cm), high stromal CD3+ TILs or high stromal CD8+ TILs were associated with better survival. However, in large tumors (≥3 cm), PD1+ TILs or high stromal CD8+ TILs carried a poorer survival. Our study implied that immune-based therapy including PD1/PD-L1 checkpoint blockade might be useful in gallbladder adenocarcinomas. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.