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Mature neutrophils ...
Mature neutrophils suppress T cell immunity in ovarian cancer microenvironment
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- Singel, Kelly L. (author)
- Roswell Park Cancer Institute
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- Emmons, Tiffany R. (author)
- Roswell Park Cancer Institute
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- Khan, Anm Nazmul H. (author)
- Roswell Park Cancer Institute
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- Mayor, Paul C. (author)
- Roswell Park Cancer Institute
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- Shen, Shichen (author)
- The State University of New York
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- Wong, Jerry T. (author)
- Roswell Park Cancer Institute
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- Morrell, Kayla (author)
- Roswell Park Cancer Institute
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- Eng, Kevin H. (author)
- Roswell Park Cancer Institute
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- Mark, Jaron (author)
- Roswell Park Cancer Institute
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- Bankert, Richard B. (author)
- The State University of New York
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- Matsuzaki, Junko (author)
- Roswell Park Cancer Institute
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- Koya, Richard C. (author)
- Roswell Park Cancer Institute
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- Blom, Anna M. (author)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups
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- McLeish, Kenneth R. (author)
- University of Louisville
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- Qu, Jun (author)
- The State University of New York
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Ram, Sanjay (author)
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- Moysich, Kirsten B. (author)
- Roswell Park Cancer Institute
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- Abrams, Scott I. (author)
- University of Massachusetts
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- Odunsi, Kunle (author)
- Roswell Park Cancer Institute
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- Zsiros, Emese (author)
- Roswell Park Cancer Institute
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- Segal, Brahm H. (author)
- Roswell Park Cancer Institute,The State University of New York
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(creator_code:org_t)
- 2019-03-07
- 2019
- English.
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In: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 4:5
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http://insight.jci.o...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Epithelial ovarian cancer (EOC) often presents with metastases and ascites. Granulocytic myeloid-derived suppressor cells are an immature population that impairs antitumor immunity. Since suppressive granulocytes in the ascites of patients with newly diagnosed EOC were morphologically mature, we hypothesized that PMN were rendered suppressive in the tumor microenvironment (TME). Circulating PMN from patients were not suppressive but acquired a suppressor phenotype (defined as ≥1 log10 reduction of anti-CD3/CD28-stimulated T cell proliferation) after ascites supernatant exposure. Ascites supernatants (20 of 31 supernatants) recapitulated the suppressor phenotype in PMN from healthy donors. T cell proliferation was restored with ascites removal and restimulation. PMN suppressors also inhibited T cell activation and cytokine production. PMN suppressors completely suppressed proliferation in naive, central memory, and effector memory T cells and in engineered tumor antigen-specific cytotoxic T lymphocytes, while antigen-specific cell lysis was unaffected. Inhibition of complement C3 activation and PMN effector functions, including CR3 signaling, protein synthesis, and vesicular trafficking, abrogated the PMN suppressor phenotype. Moreover, malignant effusions from patients with various metastatic cancers also induced the C3-dependent PMN suppressor phenotype. These results point to PMN impairing T cell expansion and activation in the TME and the potential for complement inhibition to abrogate this barrier to antitumor immunity.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Complement
- Immunology
- Neutrophils
- Oncology
- T cells
Publication and Content Type
- art (subject category)
- ref (subject category)
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To the university's database
- By the author/editor
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Singel, Kelly L.
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Emmons, Tiffany ...
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Khan, Anm Nazmul ...
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Mayor, Paul C.
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Shen, Shichen
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Wong, Jerry T.
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show more...
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Morrell, Kayla
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Eng, Kevin H.
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Mark, Jaron
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Bankert, Richard ...
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Matsuzaki, Junko
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Koya, Richard C.
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Blom, Anna M.
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McLeish, Kenneth ...
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Qu, Jun
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Ram, Sanjay
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Moysich, Kirsten ...
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Abrams, Scott I.
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Odunsi, Kunle
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Zsiros, Emese
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Segal, Brahm H.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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JCI Insight
- By the university
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Lund University