PD-1/PD-L1-Associated Immunoarchitectural Patterns Stratify Pancreatic Cancer Patients into Prognostic/Predictive Subgroups.

Karamitopoulou, Eva; Andreou, Andreas; Pahud de Mortanges, Aurélie; Tinguely, Marianne; Gloor, Beat; Perren, Aurel (2021). PD-1/PD-L1-Associated Immunoarchitectural Patterns Stratify Pancreatic Cancer Patients into Prognostic/Predictive Subgroups. Cancer immunology research, 9(12), pp. 1439-1450. American Association for Cancer Research 10.1158/2326-6066.CIR-21-0144

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Immunotherapy, including PD-1/PD-L1 agonists, has shown limited efficacy in pancreatic ductal adenocarcinoma (PDAC). We examined the PD-1/PD-L1 expression and immunoarchitectural features by automated morphometric analysis using multiplex immunofluorescence and 118 microsatellite-stable, treatment-naïve, surgically resected PDACs (study cohort). Five microsatellite-instable cases were stained in parallel (MSI cohort). Molecular analysis was additionally performed. An independent PDAC cohort (n = 226) was immunostained for PD-L1 and used as a validation cohort. PD-L1 expression on tumor cells (TC) and/or immune cells (IC) was present in 32% and 30% of the study and validation cohorts, respectively, and assigned into one of four patterns: "adaptive-1" (TC: 0, IC > 1%), "adaptive-2" (TC > 1% to < 25%, IC > 1%), "constitutive" (TC ≥ 25%, IC: 0), and "combined" (TC ≥ 25%, IC > 1%). "Constitutive" tumors were characterized by reduced numbers of all ICs and poor outcome. In contrast, "adaptive-1" tumors exhibited abundant T cells, including high counts of cytotoxic CD3+CD8+ and PD-1+CD3+CD8+ cells, but low counts of PD-L1+CD3+CD8+ cells and associated with the best outcome. "Adaptive-2" tumors displayed higher proportions of PD-L1+CD3+CD8+ T cells and tumor-associated macrophages (CD68+ and CD68+CD206+) compared with "adaptive-1" tumors. In the "combined" pattern, extensive PD-L1 expression on TCs was accompanied by increased numbers of T cells and improved overall survival. ICs were closer to PD-L1- than to PD-L1+ PDAC cells. TP53 and PIK3CA alterations tended to be more frequent in PD-L1+ tumors. The 5 MSI cases were PD-L1- The distinct PD-1/PD-L1-associated immunoarchitectural patterns underpin the heterogeneity of the immunologic responses and might be used to inform patient outcomes and therapeutic decisions in pancreatic cancer.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Service Sector > Institute of Pathology > Tissue Bank Bern 04 Faculty of Medicine > Service Sector > Institute of Pathology 04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery 04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine 04 Faculty of Medicine > Service Sector > Institute of Pathology > Translational Research Unit
UniBE Contributor:	Andreou, Andreas, Gloor, Beat, Perren, Aurel
Subjects:	500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health
ISSN:	2326-6074
Publisher:	American Association for Cancer Research
Language:	English
Submitter:	Aurel Perren
Date Deposited:	03 Dec 2021 07:21
Last Modified:	05 Dec 2022 15:54
Publisher DOI:	10.1158/2326-6066.CIR-21-0144
PubMed ID:	34526323
URI:	https://boris.unibe.ch/id/eprint/160935