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Lack of immunoediting in murine pancreatic cancer reversed with neoantigen.

Evans, Rebecca A; Diamond, Mark S; Rech, Andrew J; Chao, Timothy; Richardson, Max W; Lin, Jeffrey H; Bajor, David L; Byrne, Katelyn T; Stanger, Ben Z; Riley, James L; Markosyan, Nune; Winograd, Rafael; Vonderheide, Robert H.
JCI Insight; 1(14)2016 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-27642636
In carcinogen-driven cancers, a high mutational burden results in neoepitopes that can be recognized immunologically. Such carcinogen-induced tumors may evade this immune response through "immunoediting," whereby tumors adapt to immune pressure and escape T cell-mediated killing. Many tumors lack a high neoepitope burden, and it remains unclear whether immunoediting occurs in such cases. Here, we evaluated T cell immunity in an autochthonous mouse model of pancreatic cancer and found a low mutational burden, absence of predicted neoepitopes derived from tumor mutations, and resistance to checkpoint immunotherapy. Spontaneous tumor progression was identical in the presence or absence of T cells. Moreover, tumors arising in T cell-depleted mice grew unchecked in immune-competent hosts. However, introduction of the neoantigen ovalbumin (OVA) led to tumor rejection and T cell memory, but this did not occur in OVA immune-tolerant mice. Thus, immunoediting does not occur in this mouse model - a likely consequence, not a cause, of absent neoepitopes. Because many human tumors also have a low missense mutational load and minimal neoepitope burden, our findings have clinical implications for the design of immunotherapy for patients with such tumors.
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