Conversion of tumor-specific CD4+ T-cell tolerance to
T-cell priming through in vivo ligation of CD40
Eduardo M. Sotomayor1, Ivan Borrello1, Erev Tubb1, Frédérique-Marie Rattis1, Harold Bien1, Zhengbin Lu1, Steve Fein1, Stephen Schoenberger2
& Hyam I. Levitsky1
1
Department of Oncology, Johns Hopkins University School
of Medicine, 720 Rutland Avenue, Ross Building, Room 347,
Baltimore, Maryland 21205, USA
2
Division of Immune Regulation, La Jolla Institute for
Allergy and Immunology, 10355 Science Center Drive, San Diego, California 92121, USA
Correspondence should be addressed to Hyam I. Levitsky
Tumor antigen-specific T-cell tolerance limits the efficacy of therapeutic
cancer vaccines. Antigen-presenting cells mediate the induction of T-cell
tolerance to self-antigens. We therefore assessed the fate of tumor-specific
CD4+ T cells in tumor-bearing recipients after in vivo
activation of antigen-presenting cells with antibodies against CD40. Such
treatment not only preserved the responsiveness of this population, but resulted
in their endogenous activation. Established tumors regressed in vaccinated
mice treated with antibody against CD40 at a time when no response was achieved
with vaccination alone. These results indicate that modulation of antigen-presenting
cells may be a useful strategy for enhancing responsiveness to immunization.
