Title: Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer.

Authors: Eruslanov, Evgeniy B; Bhojnagarwala, Pratik S; Quatromoni, Jon G; Stephen, Tom Li; Ranganathan, Anjana; Deshpande, Charuhas; Akimova, Tatiana; Vachani, Anil; Litzky, Leslie; Hancock, Wayne W; Conejo-Garcia, José R; Feldman, Michael; Albelda, Steven M; Singhal, Sunil

Published In J Clin Invest, (2014 Dec)

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(lo)CD54(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.

PubMed ID: 25384214

MeSH Terms: Antigens, CD/immunology; Cell Proliferation*; Cytokines/immunology; Humans; Lung Neoplasms/immunology*; Lung Neoplasms/pathology; Male; Neoplasm Staging; Neutrophil Activation*; Neutrophils/immunology*; Neutrophils/pathology; Receptors, Chemokine/immunology; T-Lymphocytes/immunology*; T-Lymphocytes/pathology