Multimodal mapping of the tumor and peripheral blood immune landscape in human pancreatic cancer
Menée à l'aide d'échantillons sanguins, de tissus tumoraux et de tissus adjacents prélevés sur des patients atteints d'un adénocarcinome canalaire du pancréas et menée à l'aide d'une technique de cytométrie de masse, d'immunohistochimie multiplex et de séquençage de petits ARNs cytoplasmiques, cette étude analyse les caractéristiques immunitaires de la tumeur et de son environnement
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.
Nature Cancer , résumé, 2020