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Robust anti-tumor immunity and memory in Rag-1-deficient mice following adoptive transfer of cytokine-primed splenocytes and tumor CD80 expression

Journal Article


Abstract


  • Successful immunotherapy of solid tumors has proven difficult to achieve. The aim of the current study was to further investigate the effects of peripheral CD80-mediated co-stimulation on the efficacy of polyclonal anti-tumor effector CTL in an adoptive transfer model. Splenocytes obtained from wild-type mice immunized with CD80-transduced EL4 tumor cells were expanded in vitro in the presence of either IL-12 or IL-15 and irradiated CD80-transduced EL4 tumor cells. Polyclonal CD8 T cells were the major subset in the effector population. Primed effector cells were adoptively transferred into immuno-deficient Rag-1-deficient mice which were then challenged with syngeneic vector-control or CD80-transduced EL4 tumor cells. Expression of CD80 enhanced the elimination of EL4 tumors and mouse survival. Both IL-12 and IL-15 cultured cells had enhanced cytotoxicity. Importantly, anti-tumor memory was maintained without tumor evasion following re-challenge with either CD80-transduced and vector-control EL4 cells. We also show, using antibody-mediated depletion, that endogenous NK cells present in Rag-1-deficient mice exert anti-EL4 tumor activity that is enhanced by CD80 expression. Collectively these data show that peripheral co-stimulation by tumor expression of CD80 results in enhanced anti-tumor efficacy of NK and polyclonal effector T cells, and suggest that TCR repertoire diversity helps protect against tumor escape and provides memory with resultant robust immunity to subsequent tumor challenge irrespective of CD80 status.

Authors


  •   Ganesan, Priyadarshini (external author)
  •   Alexander, Stephen I. (external author)
  •   Watson, Debbie
  •   Logan, Grant (external author)
  •   Zhang, Geoff Yu. (external author)
  •   Alexander, Ian (external author)

Publication Date


  • 2007

Citation


  • Ganesan, P. L., Alexander, S. I., Watson, D., Logan, G. J., Zhang, G. Y. & Alexander, I. E. (2007). Robust anti-tumor immunity and memory in Rag-1-deficient mice following adoptive transfer of cytokine-primed splenocytes and tumor CD80 expression. Cancer Immunology Immunotherapy, 56 (12), 1955-1965.

Scopus Eid


  • 2-s2.0-34848828879

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/1449

Has Global Citation Frequency


Number Of Pages


  • 10

Start Page


  • 1955

End Page


  • 1965

Volume


  • 56

Issue


  • 12

Place Of Publication


  • Germany

Abstract


  • Successful immunotherapy of solid tumors has proven difficult to achieve. The aim of the current study was to further investigate the effects of peripheral CD80-mediated co-stimulation on the efficacy of polyclonal anti-tumor effector CTL in an adoptive transfer model. Splenocytes obtained from wild-type mice immunized with CD80-transduced EL4 tumor cells were expanded in vitro in the presence of either IL-12 or IL-15 and irradiated CD80-transduced EL4 tumor cells. Polyclonal CD8 T cells were the major subset in the effector population. Primed effector cells were adoptively transferred into immuno-deficient Rag-1-deficient mice which were then challenged with syngeneic vector-control or CD80-transduced EL4 tumor cells. Expression of CD80 enhanced the elimination of EL4 tumors and mouse survival. Both IL-12 and IL-15 cultured cells had enhanced cytotoxicity. Importantly, anti-tumor memory was maintained without tumor evasion following re-challenge with either CD80-transduced and vector-control EL4 cells. We also show, using antibody-mediated depletion, that endogenous NK cells present in Rag-1-deficient mice exert anti-EL4 tumor activity that is enhanced by CD80 expression. Collectively these data show that peripheral co-stimulation by tumor expression of CD80 results in enhanced anti-tumor efficacy of NK and polyclonal effector T cells, and suggest that TCR repertoire diversity helps protect against tumor escape and provides memory with resultant robust immunity to subsequent tumor challenge irrespective of CD80 status.

Authors


  •   Ganesan, Priyadarshini (external author)
  •   Alexander, Stephen I. (external author)
  •   Watson, Debbie
  •   Logan, Grant (external author)
  •   Zhang, Geoff Yu. (external author)
  •   Alexander, Ian (external author)

Publication Date


  • 2007

Citation


  • Ganesan, P. L., Alexander, S. I., Watson, D., Logan, G. J., Zhang, G. Y. & Alexander, I. E. (2007). Robust anti-tumor immunity and memory in Rag-1-deficient mice following adoptive transfer of cytokine-primed splenocytes and tumor CD80 expression. Cancer Immunology Immunotherapy, 56 (12), 1955-1965.

Scopus Eid


  • 2-s2.0-34848828879

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/1449

Has Global Citation Frequency


Number Of Pages


  • 10

Start Page


  • 1955

End Page


  • 1965

Volume


  • 56

Issue


  • 12

Place Of Publication


  • Germany