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

Cell Reports
Dania ZhivakiJonathan C Kagan

Abstract

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.

Citations

Feb 14, 2021·International Journal of Molecular Sciences·Denise van UdenRudi W Hendriks
Feb 16, 2021·Frontiers in Immunology·Bram Van Den EeckhoutSarah Gerlo
Jan 30, 2021·Nature Communications·Laetitia DouguetValérie Vouret-Craviari
Jan 8, 2021·International Journal of Molecular Sciences·Kohsuke Tsuchiya
Feb 20, 2021·Nature Immunology·Katherine A Deets, Russell E Vance
Apr 2, 2021·Frontiers in Endocrinology·Marco Di Gioia, Ivan Zanoni
Apr 14, 2021·Immunology Letters·Lukas HatscherDiana Dudziak
May 27, 2021·Trends in Immunology·Dania Zhivaki, Jonathan C Kagan
Jun 11, 2021·Nature·Karen O DixonVijay K Kuchroo
Sep 23, 2021·Nature Reviews. Immunology·Dania Zhivaki, Jonathan C Kagan
Sep 20, 2021·Journal of Molecular Biology·Sebastian Rühl, Petr Broz

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Datasets Mentioned

BETA
GSE156159

Methods Mentioned

BETA
biopsies
flow cytometry
Assay
ELISA
FCS
CLIP

Software Mentioned

Seuratv3
- Formats
Bio
R
RSEM
DESeq2
GraphPad
bcl2fastq
FlowJo
Fiji

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