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

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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-g 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.

Original languageEnglish (US)
Pages (from-to)2843-2848
Number of pages6
JournalJournal of Immunology
Issue number10
StatePublished - May 15 2019

Bibliographical note

Publisher Copyright:
Copyright © 2019 by The American Association of Immunologists, Inc.


  • Animals
  • Antigens, CD/genetics
  • CD8-Positive T-Lymphocytes/immunology
  • Female
  • Interferon-gamma/genetics
  • Lymphocytes, Tumor-Infiltrating/immunology
  • Male
  • Melanoma, Experimental/genetics
  • Mice
  • Mice, Transgenic
  • Neoplasm Proteins/genetics
  • Programmed Cell Death 1 Receptor/genetics
  • Sepsis/genetics

PubMed: MeSH publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Journal Article
  • Research Support, N.I.H., Extramural


Dive into the research topics of 'Cutting edge: Polymicrobial sepsis has the capacity to reinvigorate tumor-infiltrating CD8 T cells and prolong host survival'. Together they form a unique fingerprint.

Cite this