Cutting Edge: Polymicrobial Sepsis Has the Capacity to Reinvigorate Tumor-Infiltrating CD8 T Cells and Prolong Host Survival

Derek B Danahy; Isaac J Jensen; Thomas S Griffith; Vladimir P Badovinac

doi:10.4049/jimmunol.1900076

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Cutting Edge: Polymicrobial Sepsis Has the Capacity to Reinvigorate Tumor-Infiltrating CD8 T Cells and Prolong Host Survival

Journal article

Peer reviewed

Cutting Edge: Polymicrobial Sepsis Has the Capacity to Reinvigorate Tumor-Infiltrating CD8 T Cells and Prolong Host Survival

Derek B Danahy, Isaac J Jensen, Thomas S Griffith and Vladimir P Badovinac

The Journal of immunology (1950), Vol.202(10), pp.2843-2848

05/15/2019

DOI: 10.4049/jimmunol.1900076

PMCID: PMC6504616

PMID: 30971442

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Abstract

Malignancy increases sepsis incidence 10-fold and elevates sepsis-associated mortality. Advances in treatment have improved survival of cancer patients shortly after sepsis, but there is a paucity of information on how sepsis impacts cancer growth, development, and prognosis. To test this, cecal ligation and puncture surgery was performed on B16 melanoma-bearing mice to show that sepsis has detrimental effects in hosts with advanced tumors, leading to increased mortality. Surprisingly, mice experiencing cecal ligation and puncture-induced sepsis earlier during tumor development exhibited CD8 T cell-dependent attenuation of tumor growth. Sepsis-resistant CD8 tumor-infiltrating T cells showed increased in vivo activation, effector IFN-γ cytokine production, proliferation, and expression of activation/inhibitory PD-1/LAG-3 receptors because of a sepsis-induced liberation of tumor Ags. Sepsis-reinvigorated CD8 tumor-infiltrating T cells were also amenable to (anti-PD-L1/LAG-3) checkpoint blockade therapy, further prolonging cancer-associated survival in sepsis survivors. Thus, sepsis has the capacity to improve tumor-specific CD8 T cell responses, leading to better cancer prognosis and increased survival.

Animals

Antigens, CD - genetics

Antigens, CD - immunology

CD8-Positive T-Lymphocytes - immunology

CD8-Positive T-Lymphocytes - pathology

Female

Interferon-gamma - genetics

Interferon-gamma - immunology

Lymphocytes, Tumor-Infiltrating - immunology

Lymphocytes, Tumor-Infiltrating - pathology

Male

Melanoma, Experimental - genetics

Melanoma, Experimental - immunology

Melanoma, Experimental - pathology

Mice

Mice, Transgenic

Neoplasm Proteins - genetics

Neoplasm Proteins - immunology

Programmed Cell Death 1 Receptor - genetics

Programmed Cell Death 1 Receptor - immunology

Sepsis - genetics

Sepsis - immunology

Sepsis - microbiology

Sepsis - pathology

Details

Title: Subtitle: Cutting Edge: Polymicrobial Sepsis Has the Capacity to Reinvigorate Tumor-Infiltrating CD8 T Cells and Prolong Host Survival
Creators: Derek B Danahy - University of Iowa
Isaac J Jensen - University of Iowa
Thomas S Griffith - University of Minnesota
Vladimir P Badovinac - University of Iowa
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.202(10), pp.2843-2848
DOI: 10.4049/jimmunol.1900076
PMID: 30971442
PMCID: PMC6504616
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: I01 BX001324 / BLRD VA T32 AI007511 / NIAID NIH HHS R01 AI114543 / NIAID NIH HHS T32 AI007485 / NIAID NIH HHS R01 GM113961 / NIGMS NIH HHS R01 AI042767 / NIAID NIH HHS P30 CA086862 / NCI NIH HHS R01 GM115462 / NIGMS NIH HHS
Language: English
Date published: 05/15/2019
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984181073502771

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