Multimodal Mapping of the Tumor and Peripheral Blood Immune Landscape in Human Pancreatic Cancer

• Published in: Nature cancer Vol. 1; no. 11; p. 1097
• Main Authors: Steele, Nina G, Carpenter, Eileen S, Kemp, Samantha B, Sirihorachai, Veerin R, The, Stephanie, Delrosario, Lawrence, Lazarus, Jenny, Amir, El-Ad David, Gunchick, Valerie, Espinoza, Carlos, Bell, Samantha, Harris, Lindsey, Lima, Fatima, Irizarry-Negron, Valerie, Paglia, Daniel, Macchia, Justin, Chu, Angel Ka Yan, Schofield, Heather, Wamsteker, Erik-Jan, Kwon, Richard, Schulman, Allison, Prabhu, Anoop, Law, Ryan, Sondhi, Arjun, Yu, Jessica, Patel, Arpan, Donahue, Katelyn, Nathan, Hari, Cho, Clifford, Anderson, Michelle A, Sahai, Vaibhav, Lyssiotis, Costas A, Zou, Weiping, Allen, Benjamin L, Rao, Arvind, Crawford, Howard C, Bednar, Filip, Frankel, Timothy L, Pasca di Magliano, Marina
• Format: Journal Article
• Language: English
• Published: England 01.11.2020
• Subjects: CD8-Positive T-Lymphocytes - pathology; Humans; Pancreatic Neoplasms - pathology; Tumor Microenvironment - genetics; CD8+ T cells; pancreatic cancer; tumor immunology; TIGIT; Single-cell RNA sequencing; immune checkpoints
• ISSN: 2662-1347
• DOI: 10.1038/s43018-020-00121-4

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.