Inflammasomes within Hyperactive Murine Dendritic Cells Stimulate Long-Lived T Cell-Mediated Anti-tumor Immunity

Dania Zhivaki; Francesco Borriello; Ohn A. Chow; Benjamin Doran; Ira Fleming; Derek J. Theisen; Paris Pallis; Alex K. Shalek; Caroline L. Sokol; Ivan Zanoni; Jonathan C. Kagan

Cell Reports (Nov 2020)

Inflammasomes within Hyperactive Murine Dendritic Cells Stimulate Long-Lived T Cell-Mediated Anti-tumor Immunity

Dania Zhivaki,
Francesco Borriello,
Ohn A. Chow,
Benjamin Doran,
Ira Fleming,
Derek J. Theisen,
Paris Pallis,
Alex K. Shalek,
Caroline L. Sokol,
Ivan Zanoni,
Jonathan C. Kagan

Affiliations

Dania Zhivaki: Harvard Medical School and Division of Gastroenterology, Boston Children’s Hospital, Boston, MA, USA
Francesco Borriello: Harvard Medical School and Division of Immunology, Boston Children’s Hospital, Boston, MA, USA; Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy
Ohn A. Chow: Center for Immunology & Inflammatory Diseases, Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Benjamin Doran: Department of Chemistry, Institute for Medical Engineering and Sciences (IMES), Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02142, USA; Ragon Institute of MGH, Harvard, and MIT, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Ira Fleming: Department of Chemistry, Institute for Medical Engineering and Sciences (IMES), Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02142, USA; Ragon Institute of MGH, Harvard, and MIT, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Derek J. Theisen: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
Paris Pallis: Department of Immunology, Harvard Medical School, Boston, MA 02115, USA
Alex K. Shalek: Department of Chemistry, Institute for Medical Engineering and Sciences (IMES), Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02142, USA; Ragon Institute of MGH, Harvard, and MIT, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Caroline L. Sokol: Center for Immunology & Inflammatory Diseases, Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Ivan Zanoni: Harvard Medical School and Division of Gastroenterology, Boston Children’s Hospital, Boston, MA, USA; Harvard Medical School and Division of Immunology, Boston Children’s Hospital, Boston, MA, USA
Jonathan C. Kagan: Harvard Medical School and Division of Gastroenterology, Boston Children’s Hospital, Boston, MA, USA; Corresponding author

Journal volume & issue: Vol. 33, no. 7
p. 108381

Abstract

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Summary: Central to anti-tumor immunity are dendritic cells (DCs), which stimulate long-lived protective T cell responses. Recent studies have demonstrated that DCs can achieve a state of hyperactivation, which is associated with inflammasome activities within living cells. Herein, we report that hyperactive DCs have an enhanced ability to migrate to draining lymph nodes and stimulate potent cytotoxic T lymphocyte (CTL) responses. This enhanced migratory activity is dependent on the chemokine receptor CCR7 and is associated with a unique transcriptional program that is not observed in conventionally activated or pyroptotic DCs. We show that hyperactivating stimuli are uniquely capable of inducing durable CTL-mediated anti-tumor immunity against tumors that are sensitive or resistant to PD-1 inhibition. These protective responses are intrinsic to the cDC1 subset of DCs, depend on the inflammasome-dependent cytokine IL-1β, and enable tumor lysates to serve as immunogens. If these activities are verified in humans, hyperactive DCs may impact immunotherapy.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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