Multimodal mapping of the tumor and peripheral blood immune landscape in human pancreatic cancer
Top Cited Papers
- 26 October 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Cancer
- Vol. 1 (11), 1097-1112
- https://doi.org/10.1038/s43018-020-00121-4
Abstract
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 patients’ T cells and increased markers of CD8+ T cell dysfunction in the 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 TIGIT, 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.Keywords
Funding Information
- American Cancer Society (PF-19-096-01, RSG-16-005-01)
- American College of Gastroenterology (T32-DK094775)
- U.S. Department of Health & Human Services | National Institutes of Health (GM113900, CA009676, CA046592, CA201581)
- U.S. Department of Health & Human Services | NIH | National Cancer Institute (CA214955, CA151588, CA198074, CA224145)
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