CD95-mediated tumor recognition by CD4+ effector cells in a murine mammary model

Etsuko Aruga, Keishi Tanigawa, Atsushi Aruga, Hiroshi Arai, John W. Smith, Brian J. Nickoloff, Gary J. Nabel, Alfred E. Chang

Research output: Contribution to journalArticlepeer-review

Abstract

The authors examined cellular mechanisms involved in anti-tumor reactivity induced by the murine MT-9G1 mammary tumor line, which was transduced to secrete granulocyte macrophage-colony-stimulating factor (GM- CSF). Compared with the parental MT-901 tumor, MT-9G1 subcutaneous tumors elicited an influx of CD4+ cells and dendritic cells. Secondary in vitro activation of tumor-draining lymph node cells with anti-CD3 and interleukin-2 resulted in effector cells that can mediate regression of established pulmonary metastases after adoptive transfer. In vivo depletion of T-cell subsets showed that tumor regression required CD4+ tumor-draining lymph node cells rather than CD8+ cells. The activated CD4+ cells expressed CD95L and mediated lysis of CD95+ MT-901 tumor cells, which were major histocompatibility complex class II negative. The CD4+ cells also released GM-CSF in response to tumor stimulation. A Fas fusion protein inhibited tumor lysis and GM-CSF release by the CD4+ cells. These studies document an alternate pathway by which CD4+ immune cells may recognize major histocompatibility complex class II-deficient tumors in which CD95L-bearing T cells induced an anti-tumor response mediated via CD95L:CD95.

Original languageEnglish (US)
Pages (from-to)225-234
Number of pages10
JournalJournal of Immunotherapy
Volume23
Issue number2
DOIs
StatePublished - Mar 2000
Externally publishedYes

Keywords

  • Adoptive immunotherapy
  • Breast neoplasm
  • Fas
  • FasL
  • T cells

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

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