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Abstract 3707: Tumor-associated neutrophils with antigen-presenting features in early-stage human lung cancer

Publication ,  Conference
Stadanlick, J; Rao, A; Annunziata, M; Moon, E; O'brien, S; Bhojnagarwala, P; Feldman, M; Hancock, W; Conejo-Garcia, J; Singhal, S; Albelda, S ...
Published in: Cancer Research
July 1, 2017

To date there has been an increasing focus on the interactions between inflammatory myeloid cells and T cells in the tumor microenvironment because cytotoxic anti-tumoral T cells represent the chief effector mechanism of anti-tumoral immunity. Tumor-associated neutrophils (TANs) represent a significant portion of inflammatory cells in lung tumors; however, whether specialized neutrophil subpopulations capable of regulating T cell responses exist in human cancers is unknown. Our goal was to identify subsets of TANs and determine their specific roles in the regulation of T cell responses in patients with early stage lung cancer. An extensive phenotypic analysis of 55 early-stage human lung tumors revealed that TANs, defined as CD11b+Arg1+MPO+CD66b+CD15+ cells, contained two major sub-populations. One subset of “canonical” TANs expressed classic neutrophil markers. A second subset of TANs displayed a combination of neutrophil markers plus markers (CD14+HLA-DR+CCR7+CD86+) normally expressed on antigen-presenting cells (APC). We termed this unique neutrophil population “APC-like hybrid TANs”. The frequency of these hybrid TANs varied widely within lung cancers and ranged from 0.5-25% of all TANs. Interestingly, the frequency of this hybrid population declined as tumors enlarged, and they were almost completely absent in tumors greater than 5 cm in diameter. Mechanistically, we determined that low doses of IFN-γ and GM-CSF in the tumors were required for the development of APC-like hybrid neutrophils. The high proportion of hybrid TANs (>10% of all TANs) directly correlated with the presence of IFN-γ and GM-CSF in the autologous tumor tissue. Using bone marrow-derived immature granulocytes, which were found to have prolonged survival in vitro, we discovered that these APC-like hybrid neutrophils originate from CD11b+CD15+CD10-CD16-/low/int neutrophil progenitors in the presence of IFN-γ and GM-CSF or in tumor-conditioned media. Functionally, the APC-like hybrid neutrophils are superior to canonical neutrophils in their ability to: 1) stimulate antigen non-specific autologous T cell responses 2) directly stimulate antigen-specific autologous memory T cell responses, 4) augment NY-ESO-1 specific effector T cell responses by providing a co-stimulatory signals through the OX40L, 4-1BBL CD86, CD54 molecules, and 5) cross present tumor-associated antigen as IgG-immune complex. In summary, we provide the first evidence of two subsets of TANs in lung cancer. All TANs had an activated phenotype and could support (rather than inhibit) T cell functions to some degree. However, we identified a subset of TAN in early-stage lung tumors that can undergo a unique differentiation process resulting in formation of specialized subset of APC-like hybrid neutrophils. These hybrid neutrophils may provide new opportunities to boost the efficacy of vaccines based on cytotoxic T lymphocyte inductionCitation Format: Jason Stadanlick, Abhishek Rao, Michael Annunziata, Edmund Moon, Shaun O'brien, Pratik Bhojnagarwala, Michael Feldman, Wayne Hancock, Jose Conejo-Garcia, Sunil Singhal, Stephen Albelda, Evgeniy Eruslanov. Tumor-associated neutrophils with antigen-presenting features in early-stage human lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3707. doi:10.1158/1538-7445.AM2017-3707

Duke Scholars

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

July 1, 2017

Volume

77

Issue

13_Supplement

Start / End Page

3707 / 3707

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis
 

Citation

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Stadanlick, J., Rao, A., Annunziata, M., Moon, E., O’brien, S., Bhojnagarwala, P., … Eruslanov, E. (2017). Abstract 3707: Tumor-associated neutrophils with antigen-presenting features in early-stage human lung cancer. In Cancer Research (Vol. 77, pp. 3707–3707). American Association for Cancer Research (AACR). https://doi.org/10.1158/1538-7445.am2017-3707
Stadanlick, Jason, Abhishek Rao, Michael Annunziata, Edmund Moon, Shaun O’brien, Pratik Bhojnagarwala, Michael Feldman, et al. “Abstract 3707: Tumor-associated neutrophils with antigen-presenting features in early-stage human lung cancer.” In Cancer Research, 77:3707–3707. American Association for Cancer Research (AACR), 2017. https://doi.org/10.1158/1538-7445.am2017-3707.
Stadanlick J, Rao A, Annunziata M, Moon E, O’brien S, Bhojnagarwala P, et al. Abstract 3707: Tumor-associated neutrophils with antigen-presenting features in early-stage human lung cancer. In: Cancer Research. American Association for Cancer Research (AACR); 2017. p. 3707–3707.
Stadanlick, Jason, et al. “Abstract 3707: Tumor-associated neutrophils with antigen-presenting features in early-stage human lung cancer.” Cancer Research, vol. 77, no. 13_Supplement, American Association for Cancer Research (AACR), 2017, pp. 3707–3707. Crossref, doi:10.1158/1538-7445.am2017-3707.
Stadanlick J, Rao A, Annunziata M, Moon E, O’brien S, Bhojnagarwala P, Feldman M, Hancock W, Conejo-Garcia J, Singhal S, Albelda S, Eruslanov E. Abstract 3707: Tumor-associated neutrophils with antigen-presenting features in early-stage human lung cancer. Cancer Research. American Association for Cancer Research (AACR); 2017. p. 3707–3707.

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

July 1, 2017

Volume

77

Issue

13_Supplement

Start / End Page

3707 / 3707

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis