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Multimodal Mapping of the Tumor and Peripheral Blood Immune Landscape in Human Pancreatic Cancer.
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.
Afiliação
  • Steele NG; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
  • Carpenter ES; Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA.
  • Kemp SB; Molecular and Cellular Pathology Graduate Program, University of Michigan, Ann Arbor, MI, USA.
  • Sirihorachai VR; Cancer Biology Program, University of Michigan, Ann Arbor, MI, USA.
  • The S; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Delrosario L; Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
  • Lazarus J; Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
  • Amir ED; Astrolabe Diagnostics, Fort Lee, NJ, USA.
  • Gunchick V; Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA.
  • Espinoza C; Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
  • Bell S; Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
  • Harris L; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
  • Lima F; Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
  • Irizarry-Negron V; Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
  • Paglia D; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
  • Macchia J; Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
  • Chu AKY; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Schofield H; Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
  • Wamsteker EJ; Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA.
  • Kwon R; Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA.
  • Schulman A; Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA.
  • Prabhu A; Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA.
  • Law R; Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA.
  • Sondhi A; Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA.
  • Yu J; Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA.
  • Patel A; Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA.
  • Donahue K; Cancer Biology Program, University of Michigan, Ann Arbor, MI, USA.
  • Nathan H; Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
  • Cho C; Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
  • Anderson MA; Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA.
  • Sahai V; Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA.
  • Lyssiotis CA; Molecular and Cellular Pathology Graduate Program, University of Michigan, Ann Arbor, MI, USA.
  • Zou W; Cancer Biology Program, University of Michigan, Ann Arbor, MI, USA.
  • Allen BL; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
  • Rao A; Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
  • Crawford HC; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
  • Bednar F; Cancer Biology Program, University of Michigan, Ann Arbor, MI, USA.
  • Frankel TL; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Pasca di Magliano M; Michigan Institute of Data Science (MIDAS), University of Michigan, Ann Arbor, MI, USA.
Nat Cancer ; 1(11): 1097-1112, 2020 11.
Article em En | MEDLINE | ID: mdl-34296197
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 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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Linfócitos T CD8-Positivos Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Linfócitos T CD8-Positivos Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article