title: Lack of immunoediting in murine pancreatic cancer reversed with neoantigen.
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.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Evans
authors.forename: Mark S
authors.initials: MS
authors.lastname: Diamond
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Rech
authors.forename: Timothy
authors.initials: T
authors.lastname: Chao
authors.forename: Max W
authors.initials: MW
authors.lastname: Richardson
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lin
authors.forename: David L
authors.initials: DL
authors.lastname: Bajor
authors.forename: Katelyn T
authors.initials: KT
authors.lastname: Byrne
authors.forename: Ben Z
authors.initials: BZ
authors.lastname: Stanger
authors.forename: James L
authors.initials: JL
authors.lastname: Riley
authors.forename: Nune
authors.initials: N
authors.lastname: Markosyan
authors.forename: Rafael
authors.initials: R
authors.lastname: Winograd
authors.forename: Robert H
authors.initials: RH
authors.lastname: Vonderheide
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D045744:Cell Line, Tumor; D000939:Epitopes / Q000276:immunology; D005260:Female; D057131:Immune Evasion; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D010190:Pancreatic Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D000939:Epitopes