Journal article
Cutting Edge: Polymicrobial Sepsis Has the Capacity to Reinvigorate Tumor-Infiltrating CD8 T Cells and Prolong Host Survival
The Journal of immunology (1950), Vol.202(10), pp.2843-2848
05/15/2019
DOI: 10.4049/jimmunol.1900076
PMCID: PMC6504616
PMID: 30971442
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.
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 IowaIsaac J Jensen - University of IowaThomas S Griffith - University of MinnesotaVladimir 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
- 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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