Peptide Prevention

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Science  10 May 2013:
Vol. 340, Issue 6133, pp. 662
DOI: 10.1126/science.340.6133.662-b

One of the many challenges faced by cancer survivors is the possibility of relapse. Theories as to why cancers relapse after initially responding to therapy are varied and are likely to depend, at least in part, on the type of treatment the patient receives. Engels et al. investigated why tumors relapse after successful adoptive T cell therapy in mice. Mice received an injection of a fibrosarcoma cell line that expressed one of a series of defined peptide antigens. Once tumors were established, they were then treated with T cells specific for that antigen. In vitro, T cells killed the tumor cells independent of the peptide's affinity for binding to major histocompatibility complex (MHC), which presents the peptide to T cells. In vivo, however, only mice that received tumors expressing peptides that were able to bind to MHC with high affinity remained cancer-free. Relapse was observed when affinities were less than 10 nM and was associated with less efficient cross-presentation of peptide antigens by stromal cells surrounding the tumor and reduced stromal cell death. Thus, strong interactions between peptide antigens and MHC may prevent relapse by promoting robust T cell responses that target the tumor itself and the surrounding tissue.

Cancer Cell 23, 516 (2013).

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