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

Publication ,  Journal Article
Eruslanov, EB; Bhojnagarwala, PS; Quatromoni, JG; Stephen, TL; Ranganathan, A; Deshpande, C; Akimova, T; Vachani, A; Litzky, L; Hancock, WW ...
Published in: J Clin Invest
December 2014

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.

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

December 2014

Volume

124

Issue

12

Start / End Page

5466 / 5480

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Receptors, Chemokine
  • Neutrophils
  • Neutrophil Activation
  • Neoplasm Staging
  • Male
  • Lung Neoplasms
  • Immunology
  • Humans
  • Cytokines
 

Citation

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Eruslanov, E. B., Bhojnagarwala, P. S., Quatromoni, J. G., Stephen, T. L., Ranganathan, A., Deshpande, C., … Singhal, S. (2014). Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer. J Clin Invest, 124(12), 5466–5480. https://doi.org/10.1172/JCI77053
Eruslanov, Evgeniy B., Pratik S. Bhojnagarwala, Jon G. Quatromoni, Tom Li Stephen, Anjana Ranganathan, Charuhas Deshpande, Tatiana Akimova, et al. “Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer.J Clin Invest 124, no. 12 (December 2014): 5466–80. https://doi.org/10.1172/JCI77053.
Eruslanov EB, Bhojnagarwala PS, Quatromoni JG, Stephen TL, Ranganathan A, Deshpande C, et al. Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer. J Clin Invest. 2014 Dec;124(12):5466–80.
Eruslanov, Evgeniy B., et al. “Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer.J Clin Invest, vol. 124, no. 12, Dec. 2014, pp. 5466–80. Pubmed, doi:10.1172/JCI77053.
Eruslanov EB, Bhojnagarwala PS, Quatromoni JG, Stephen TL, Ranganathan A, Deshpande C, Akimova T, Vachani A, Litzky L, Hancock WW, Conejo-Garcia JR, Feldman M, Albelda SM, Singhal S. Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer. J Clin Invest. 2014 Dec;124(12):5466–5480.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

December 2014

Volume

124

Issue

12

Start / End Page

5466 / 5480

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Receptors, Chemokine
  • Neutrophils
  • Neutrophil Activation
  • Neoplasm Staging
  • Male
  • Lung Neoplasms
  • Immunology
  • Humans
  • Cytokines