DC-HIL-expressing myelomonocytic cells are critical promoters of melanoma growth

Jin Sung Chung, Kyoichi Tamura, Ponciano D Cruz, Kiyoshi Ariizumi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

A major barrier to successful cancer immunotherapy is the tumor's ability to induce T-cell tolerance by exploiting host regulatory mechanisms. Having discovered the DC-HIL receptor, which inhibits T-cell responses by binding to syndecan-4 on effector T cells, we posited the DC-HIL/syndecan-4 pathway to have an important role in cancer promotion. Among DC-HIL+myelomonocytic cells, during growth of implanted mouse melanoma, CD11b+Gr1+cells were the most expanded population and the most potent at suppressing T-cell activation. Deletion of the DC-HIL gene or infusion of anti-DC-HIL mAb abrogated these cells' suppressor function and expansion, and markedly diminished melanoma growth and metastasis. IL-1β and IFN-γ were elevated in mice bearing melanoma, and concurrent exposure to both cytokines optimally induced DC-HIL expression by tumor-infiltrating CD11b+Gr1+cells. Ligation of DC-HIL transduced phosphorylation of its intracellular immunoreceptor tyrosine-based activation motif, which in turn induced intracellular expression of IFN-γ and inducible nitric oxide synthase (iNOS), known to mediate T-cell suppression by CD11b+Gr1+cells. Thus, DC-HIL is the critical mediator of these cells' suppressor function in melanoma-bearing mice and a potential target for improving melanoma immunotherapy.

Original languageEnglish (US)
Pages (from-to)2784-2794
Number of pages11
JournalJournal of Investigative Dermatology
Volume134
Issue number11
DOIs
StatePublished - Nov 5 2014

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T-cells
Melanoma
Bearings (structural)
Syndecan-4
T-Lymphocytes
Growth
Tumors
Immunotherapy
Chemical activation
Neoplasms
Immunoreceptor Tyrosine-Based Activation Motif
Phosphorylation
Cell growth
Nitric Oxide Synthase Type II
Interleukin-1
Tyrosine
Genes
Ligation
Cytokines
Neoplasm Metastasis

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

DC-HIL-expressing myelomonocytic cells are critical promoters of melanoma growth. / Chung, Jin Sung; Tamura, Kyoichi; Cruz, Ponciano D; Ariizumi, Kiyoshi.

In: Journal of Investigative Dermatology, Vol. 134, No. 11, 05.11.2014, p. 2784-2794.

Research output: Contribution to journalArticle

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