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IL8, Neutrophils, and NETs in a Collusion against Cancer Immunity and Immunotherapy.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2021 May 01; Vol. 27 (9), pp. 2383-2393. Date of Electronic Publication: 2020 Dec 29. - Publication Year :
- 2021
-
Abstract
- One of the most important mechanisms by which cancer fosters its own development is the generation of an immune microenvironment that inhibits or impairs antitumor immune responses. A cancer permissive immune microenvironment is present in a large proportion of the patients with cancer who do not respond to immunotherapy approaches intended to trigger preexisting antitumor immune responses, for instance, immune checkpoint blockade. High circulating levels of IL8 in patients with cancer quite accurately predict those who will not benefit from checkpoint-based immunotherapy. IL8 has been reported to favor cancer progression and metastases via different mechanisms, including proangiogenesis and the maintenance of cancer stem cells, but its ability to attract and functionally modulate neutrophils and macrophages is arguably one of the most important factors. IL8 does not only recruit neutrophils to tumor lesions, but also triggers the extrusion of neutrophil extracellular traps (NET). The relevance and mechanisms underlying the contribution of both neutrophils and NETs to cancer development and progression are starting to be uncovered and include both direct effects on cancer cells and changes in the tumor microenvironment, such as facilitating metastasis, awakening micrometastases from dormancy, and facilitating escape from cytotoxic immune cells. Blockade of IL8 or its receptors (CXCR1 and CXCR2) is being pursued in drug development, and clinical trials alone or in combination with anti-PD-L1 checkpoint inhibitors are already ongoing.<br /> (©2020 American Association for Cancer Research.)
- Subjects :
- Animals
Biomarkers
Cell Line, Tumor
Cytokines metabolism
Disease Management
Disease Susceptibility
Epithelial-Mesenchymal Transition
Gene Expression Regulation, Neoplastic
Humans
Immunity
Immunotherapy
Neoplasms diagnosis
Neoplasms therapy
Neutrophils pathology
Extracellular Traps immunology
Interleukin-8 metabolism
Neoplasms etiology
Neoplasms metabolism
Neutrophils immunology
Neutrophils metabolism
Tumor Microenvironment immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 27
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 33376096
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-20-1319