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Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer
- Source :
- Journal of Clinical Investigation. December 1, 2014, Vol. 124 Issue 12, p5466, 15 p.
- Publication Year :
- 2014
-
Abstract
- Infiltrating inflammatory cells are highly prevalent within the tumor microenvironment and mediate many processes associated with tumor progression; however, the contribution of specific populations remains unclear. For example, the nature and function of tumor-associated neutrophils (TANs) in the cancer microenvironment is largely unknown. The goal of this study was to provide a phenotypic and functional characterization of TANs in surgically resected lung cancer patients. We found that TANs constituted 5%-25% of cells isolated from the digested human lung tumors. Compared with blood neutrophils, TANs displayed an activated phenotype ([CD62L.sup.lo][CD54.sup.hi]) with a distinct repertoire of chemokine receptors that included CCR5, CCR7, CXCR3, and CXCR4. TANs produced substantial quantities of the proinflammatory factors MCP-1, IL-8, MIP-1α, and IL-6, as well as the antiinflammatory IL-1R antagonist. Functionally, both TANs and neutrophils isolated from distant nonmalignant lung tissue were able to stimulate T cell proliferation and IFN-γ release. Cross-talk between TANs and activated T cells led to substantial upregulation of CD54, CD86, OX40L, and 4-1BBL costimulatory molecules on the neutrophil surface, which bolstered T cell proliferation in a positive-feedback loop. Together our results demonstrate that in the earliest stages of lung cancer, TANs are not immunosuppressive, but rather stimulate T cell responses.<br />Introduction Murine and human studies suggest that tumor initiation and progression are commonly accompanied by 'smoldering' inflammation (1). Tumor-infiltrating myeloid cells represent a significant proportion of the inflammatory cell population [...]
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 124
- Issue :
- 12
- Database :
- Gale General OneFile
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.396768228
- Full Text :
- https://doi.org/10.1172/JCI77053