Journal Article

Multimodal mapping of the tumor and peripheral blood immune landscape in human pancreatic cancer

The, Stephanie, Paglia, Daniel, Anderson, Michelle A., Kemp, Samantha B., Cho, Clifford, Rao, Arvind, Espinoza, Carlos, Yu, Jessica, Lyssiotis, Costas A., Pasca di Magliano, Marina, Irizarry-Negron, Valerie, Bednar, Filip, Zou, Weiping, Macchia, Justin, Frankel, Timothy L., Crawford, Howard C., Bell, Samantha, Gunchick, Valerie, Steele, Nina G., Schofield, Heather, Sondhi, Arjun, Donahue, Katelyn, Sahai, Vaibhav, Prabhu, Anoop, Schulman, Allison, Patel, Arpan, Lazarus, Jenny, Allen, Benjamin L., Chu, Angel Ka Yan, Law, Ryan, Nathan, Hari, Lima, Fatima, Wamsteker, Erik-Jan, Harris, Lindsey, Sirihorachai, Veerin R., Delrosario, Lawrence, Carpenter, Eileen S., Amir, El-ad David, Kwon, Richard

2020

Overview

Pancreatic ductal adenocarcinoma (PDA) is characterized by an immune-suppressive tumor microenvironment that renders it largely refractory to immunotherapy. We implemented a multimodal analysis approach to elucidate the immune landscape in PDA. Using a combination of CyTOF, single-cell RNA sequencing, and multiplex immunohistochemistry on patient tumors, matched blood, and non-malignant samples, we uncovered a complex network of immune-suppressive cellular interactions. These experiments revealed heterogeneous expression of immune checkpoint receptors in individual patient's T cells and increased markers of CD8 T cell dysfunction in advanced disease stage. Tumor-infiltrating CD8 T cells had an increased proportion of cells expressing an exhausted expression profile that included upregulation of the immune checkpoint , a finding that we validated at the protein level. Our findings point to a profound alteration of the immune landscape of tumors, and to patient-specific immune changes that should be taken into account as combination immunotherapy becomes available for pancreatic cancer.

• Publisher: Nature Publishing Group
• Subject: Biopsy / CD8-Positive T-Lymphocytes - pathology / Cells / Clinical trials / Cytotoxicity / Humans / Lymphocytes / Pancreatectomy / Pancreatic cancer / Pancreatic Neoplasms - pathology / Pancreatitis / Patients / Tumor Microenvironment - genetics / Tumors