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.
Original language | English (US) |
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Pages (from-to) | 1097-1112 |
Number of pages | 16 |
Journal | Nature Cancer |
Volume | 1 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2020 |
Externally published | Yes |
ASJC Scopus subject areas
- Oncology
- Cancer Research