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

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

Research output: Contribution to journalArticle

24 Scopus citations

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, IFNγ-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.

Original languageEnglish (US)
Pages (from-to)10012-10018
Number of pages7
JournalCancer Research
Volume67
Issue number20
DOIs
StatePublished - Oct 15 2007
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Nakamura, Y., Watchmaker, P., Urban, J., Sheridan, B., Giermasz, A., Nishimura, F., Sasaki, K., Cumberland, R., Muthuswamy, R., Mailliard, R. B., Larregina, A. T., Falo, L. D., Gooding, W., Storkus, W. J., Okada, H., Hendricks, R. L., & Kalinski, P. (2007). Helper function of memory CD8+ T cells: Heterologous CD8 + T cells support the induction of therapeutic cancer immunity. Cancer Research, 67(20), 10012-10018. https://doi.org/10.1158/0008-5472.CAN-07-1735