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Tumour‐induced immune suppression: role of inflammatory mediators released by myelomonocytic cells
Author(s) -
Mao Y.,
Poschke I.,
Kiessling R.
Publication year - 2014
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12229
Subject(s) - immune system , immunology , immunotherapy , macrophage , innate immune system , cancer research , cancer immunotherapy , inflammation , medicine , myeloid , myeloid derived suppressor cell , arginase , acquired immune system , cytokine , biology , cancer , suppressor , in vitro , biochemistry , amino acid , arginine
Tumour‐induced immune dysfunction is a serious challenge to immunotherapy for cancer, and intact adaptive and innate cellular immunity is key to its success. Myelomonocytic cells have a central role in this immune suppression, and tumour‐associated macrophages, eosinophils, neutrophils and myeloid‐derived suppressor cells have all been shown to be of major importance. These myelomonocytic cells secrete a broad repertoire of inflammatory mediators providing them with powerful tools to inhibit tumour‐reactive T cells and natural killer cells; free oxygen radicals including reactive oxygen species and NO , arginase, indoleamine 2,3‐dioxygenase, prostaglandins, the pro‐inflammatory heterodimer S100A8/9 and cytokines, such as granulocyte–macrophage colony‐stimulating factor and transforming growth factor‐β, have proven particularly potent in suppressing antitumour cellular immunity. Determining which of these factors prevail in individual cancer patients and designing methods aimed at neutralization or inhibition of their effects on target tissues have the potential to greatly enhance the clinical efficacy of immunotherapy.