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 language | English (US) |
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Pages (from-to) | 225-234 |
Number of pages | 10 |
Journal | Journal of Immunotherapy |
Volume | 23 |
Issue number | 2 |
DOIs | |
State | Published - Mar 2000 |
Externally published | Yes |
Keywords
- Adoptive immunotherapy
- Breast neoplasm
- Fas
- FasL
- T cells
ASJC Scopus subject areas
- Cancer Research
- Pharmacology
- Immunology