Abstract
Background/purpose Pediatric sarcomas have a poor prognosis, recur frequently, and are not effectively treated by currently available therapy. Immunotherapy is a promising treatment modality; however, to be successful, immune tolerance must be overcome. CD4+CD25+ T cells are immunosuppressive. The authors hypothesize that immune tolerance may be overcome by eliminating the regulatory CD4+CD25+ T cells, which are induced by tumor. Methods A murine fibrosarcoma (MF), which expresses an MHC-II-restricted tumor antigen (mL26), was injected subcutaneously. CD4 + T cells were isolated and CD25+ population examined. Monoclonal antibody was used to deplete CD25+ T cells. Proliferation to mL26 was used to determine CD4+ T cell response to tumor-associated antigen (TAA). Results Depletion of CD25+ cells prevented tumor establishment. Tumor-infiltrating CD25+ T cells, which madeup 48% of CD4+ T cells in tumors, suppressed proliferation in allogeneic mixed lymphocyte reactions. Draining lymph node cells from tumor-bearing (TB) mice did not proliferate in response to mL26, whereas those from naive mice responded vigorously. Depletion of CD25+ cells before immunization restored response to mL26 in TB mice. Conclusions CD4 +CD25+ T cells induced by MF facilitate tumor establishment and maintain immune tolerance. Depletion of CD4 +CD25+ T cells may be an effective means for reversing tumor tolerance and enhancing cancer vaccines.
Original language | English (US) |
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Pages (from-to) | 941-946 |
Number of pages | 6 |
Journal | Journal of Pediatric Surgery |
Volume | 39 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2004 |
Externally published | Yes |
Keywords
- Cancer
- CD25
- immunotherapy
- T cell
- tolerance
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Surgery