Murine lung cancer induces generalized T-cell exhaustion

The Journal of Surgical Research
Rohit MittalMandy L Ford

Abstract

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. 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 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 can...Continue Reading

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Citations

Jun 23, 2015·Immunology Letters·Maria Teresa P de AquinoAnil Shanker
Feb 14, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Miro ViitalaMaija Hollmén
Jun 25, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Clara S MundryKamiya Mehla
Jun 25, 2021·Frontiers in Immunology·Zheng DengZheng Zheng
Jun 16, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alexandra M MiggelbrinkPeter E Fecci

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