[HTML][HTML] Lack of immunoediting in murine pancreatic cancer reversed with neoantigen

RA Evans, MS Diamond, AJ Rech, T Chao… - JCI insight, 2016 - ncbi.nlm.nih.gov
RA Evans, MS Diamond, AJ Rech, T Chao, MW Richardson, JH Lin, DL Bajor, KT Byrne
JCI insight, 2016ncbi.nlm.nih.gov
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 …
Abstract
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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