CD40 stimulation accelerates deletion of tumor-specific CD8(+) T cells in the absence of tumor-antigen vaccination

Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10811-6. doi: 10.1073/pnas.191371898. Epub 2001 Aug 28.


Previous work has established a role for CD40-mediated signals in eliciting helper-dependent CD8(+) T cell responses. Here we investigated the effects of in vivo CD40 stimulation on the survival and function of tumor-specific CD8(+) T cells in a mouse melanoma model system. We found that agonistic anti-CD40 antibody treatment alone of tumor-bearing mice accelerated the deletion of tumor-antigen-specific T cells. However, long-term survival and function of tumor-antigen-specific T cells could be achieved when viral immunization with tumor antigen and anti-CD40 treatment were combined. This rescue of CD8(+) T cells could not be easily replicated by inflammatory or antigen-specific stimuli alone, demonstrating the specificity of signals that regulate the deletion or survival of tumor-specific T cells. These results demonstrate that opposing effects can be elicited by CD40 stimulation in vivo and suggest the need for caution in using this treatment for cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • CD40 Antigens / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Gene Expression
  • Lymphocyte Depletion
  • Melanoma, Experimental / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation / immunology
  • Ovalbumin / genetics
  • Ovalbumin / immunology
  • T-Lymphocytes / immunology
  • Tumor Cells, Cultured
  • Vaccination
  • Vaccinia virus


  • Antigens, Neoplasm
  • CD40 Antigens
  • Ovalbumin