Loss of antigen cross-presentation after complete tumor resection is associated with the generation of protective tumor-specific CD8+ T-cell immunity
Brown, M.D., van der Most, R., Vivian, J.B., Lake, R.A., Larma, I., Robinson, B.W.S. and Currie, A.J. (2012) Loss of antigen cross-presentation after complete tumor resection is associated with the generation of protective tumor-specific CD8+ T-cell immunity. OncoImmunology, 1 (7). pp. 1084-1094.
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An incomplete understanding on the effect of surgery on tumor-specific immunity continues to hamper efforts to combine surgery with immunotherapy in the clinic. Herein, we describe the impact of tumor resection on the tumor-specific T-cell response, showing that complete tumor resection is associated with (1) a decline in the amount of cross-presented tumor antigens, (2) a decline of cytolytic tumor-specific CD8+ T cell activity, and (3) the development of systemic CD8+ T cell-mediated protective immunity. Our findings are consistent with a model whereby tumor resection releases antitumor CD8+ T cells from chronic antigen exposure, allowing a gradual differentiation toward functional antitumor memory T cells. This process depends on sentinel lymph nodes, as their removal at the time of surgery was associated with a strong negative effect on survival. We conclude that complete tumor resection provides a unique environment that boosts protective immunological memory and might provide a powerful platform for immunotherapy. Our findings also carry important implications for the design and timing of post-surgery immunotherapeutic regimens.
|Publication Type:||Journal Article|
|Murdoch Affiliation:||School of Veterinary and Biomedical Sciences|
|Copyright:||© 2012 Landes Bioscience|
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