title: Different lineages of P1A-expressing cancer cells use divergent modes of immune evasion for T-cell adoptive therapy.
abstract: Tumor evasion of T-cell immunity remains a significant obstacle to adoptive T-cell therapy. It is unknown whether the mode of immune evasion is dictated by the cancer cells or by the tumor antigens. Taking advantage of the fact that multiple lineages of tumor cells share the tumor antigen P1A, we adoptively transferred transgenic T cells specific for P1A (P1CTL) into mice with established P1A-expressing tumors, including mastocytoma P815, plasmocytoma J558, and fibrosarcoma Meth A. Although P1CTL conferred partial protection, tumors recurred in almost all mice. Analysis of the status of the tumor antigen revealed that all J558 tumors underwent antigenic drift whereas all P815 tumors experienced antigenic loss. Interestingly, although Meth A cells are capable of both antigenic loss and antigenic drift, the majority of recurrent Meth A tumors retained P1A antigen. The ability of Meth A to induce apoptosis of P1CTL in vivo alleviated the need for antigenic drift and antigenic loss. Our data showed that, in spite of their shared tumor antigen, different lineages of cancer cells use different mechanisms to evade T-cell therapy.
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, OH 43210, USA. Xue-Feng.Bai@osumc.edu
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Bai
authors.forename: Jin-Qing
authors.initials: JQ
authors.lastname: Liu
authors.forename: Pramod S
authors.initials: PS
authors.lastname: Joshi
authors.forename: Lizhong
authors.initials: L
authors.lastname: Wang
authors.forename: Lijie
authors.initials: L
authors.lastname: Yin
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Labanowska
authors.forename: Nyla
authors.initials: N
authors.lastname: Heerema
authors.forename: Pan
authors.initials: P
authors.lastname: Zheng
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D017209:Apoptosis; D002455:Cell Division; D002470:Cell Survival; D017931:DNA Primers; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013154:Spleen / Q000637:transplantation; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation*
chemical_list: D000951:Antigens, Neoplasm; D017931:DNA Primers; D011948:Receptors, Antigen, T-Cell; C076546:tumor rejection antigen P815A, mouse