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J Surg Res. 2015 May 15;195(2):541-9. doi: 10.1016/j.jss.2015.02.004. Epub 2015 Feb 12.

Murine lung cancer induces generalized T-cell exhaustion.

Author information

1
Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, Georgia.
2
Department of Infectious Diseases and Emory Critical Care Center, Emory University School of Medicine, Atlanta, Georgia.
3
Department of Surgery and Emory Transplant Center, Emory University School of Medicine, Atlanta, Georgia. Electronic address: mandy.ford@emory.edu.

Abstract

BACKGROUND:

Cancer is known to modulate tumor-specific immune responses by establishing a microenvironment that leads to the upregulation of T-cell inhibitory receptors, resulting in the progressive loss of function and eventual death of tumor-specific T-cells. However, the ability of cancer to impact the functionality of the immune system on a systemic level is much less well characterized. Because cancer is known to predispose patients to infectious complications including sepsis, we hypothesized that the presence of cancer alters pathogen-directed immune responses on a systemic level.

MATERIALS AND METHODS:

We assessed systemic T-cell coinhibitory receptor expression, cytokine production, and apoptosis in mice with established subcutaneous lung cancer tumors and in unmanipulated mice without cancer.

RESULTS:

Results indicated that the frequencies of programmed death-1-positive, B and T lymphocyte attenuator-positive, and 2B4(+) cells in both the CD4(+) and CD8(+) T-cell compartments were increased in mice with localized cancer relative to non-cancer controls, and the frequencies of both CD4(+) and CD8(+) T-cells expressing multiple different inhibitory receptors were increased in cancer animals relative to non-cancer controls. Additionally, 2B4(+)CD8(+) T-cells in cancer mice exhibited reduced interleukin-2 and interferon-γ, whereas B and T lymphocyte attenuator-positive CD8(+) T-cells in cancer mice exhibited reduced interleukin-2 and tumor necrosis factor. Conversely, CD4(+) T-cells in cancer animals demonstrated an increase in the frequency of annexin V(+) apoptotic cells.

CONCLUSIONS:

Taken together, these data suggest that the presence of cancer induces systemic T-cell exhaustion and generalized immune suppression.

KEYWORDS:

Immune dysregulation; Immunology; Inflammation; T lymphocyte

PMID:
25748104
PMCID:
PMC4417390
DOI:
10.1016/j.jss.2015.02.004
[Indexed for MEDLINE]
Free PMC Article

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