Helper function of memory CD8+ T cells: heterologous CD8+ T cells support the induction of therapeutic cancer immunity.

Abstract

In contrast to the well-established efficacy of preventive vaccines, the effectiveness of therapeutic vaccines remains limited. To develop effective vaccination regimens against cancer, we have analyzed the effect of effector and memory CD8+ T cells on the ability of dendritic cells to mediate the immunologic and antitumor effects of vaccination. We show that in contrast to effector CD8+ T cells that kill antigen-carrying dendritic cells, IFNgamma-producing memory CD8+ T cells act as "helper" cells, supporting the ability of dendritic cells to produce interleukin-12 (IL-12) p70. Promoting the interaction of tumor antigen-carrying dendritic cells with memory-type "heterologous" (tumor-irrelevant) CD8+ T cells strongly enhances the IL-12p70-dependent immunogenic and therapeutic effects of vaccination in the animals bearing established tumors. Our data show that the suppressive and helper functions of CD8+ T cells are differentially expressed at different phases of CD8+ T-cell responses. Selective performance of helper functions by memory (in contrast to effector) CD8+ T cells helps to explain the phenomenon of immune memory and facilitates the design of effective therapeutic vaccines against cancer and chronic infections.

• Authors: Yutaro Nakamura, Payal Watchmaker, Julie Urban, Brian Sheridan, Adam Giermasz, Fumihiko Nishimura, Kotaro Sasaki, Rachel Cumberland, Ravikumar Muthuswamy, Robbie B Mailliard, Adriana T Larregina, Louis D Falo, William Gooding, Walter J Storkus, Hideho Okada, Robert L Hendricks, Pawel Kalinski
• Journal: Cancer research (Cancer Res) Vol. 67 Issue 20 Pg. 10012-8 (Oct 15 2007) ISSN: 0008-5472 [Print] United States
• PMID: 17942935 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cancer Vaccines

Topics

• Adenocarcinoma (immunology, therapy)
• Animals
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (immunology, pharmacology)
• Colonic Neoplasms (immunology, therapy)
• Dendritic Cells (immunology)
• Female
• Immunologic Memory (immunology)
• Immunotherapy, Adoptive (methods)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• T-Lymphocytes, Cytotoxic (immunology)
• T-Lymphocytes, Helper-Inducer (immunology)