title: Loss of tapasin in human lung and colon cancer cells and escape from tumor-associated antigen-specific CTL recognition.
abstract: Cytotoxic T-lymphocytes (CTLs) lyse target cells after recognizing the complexes of peptides and MHC class I molecules (pMHC I) on cell surfaces. Tapasin is an essential component of the peptide-loading complex (PLC) and its absence influences the surface repertoire of MHC class I peptides. In the present study, we assessed tapasin expression in 85 primary tumor lesions of non-small cell lung cancer (NSCLC) patients, demonstrating that tapasin expression positively correlated with patient survival. CD8+T-cell infiltration of tumor lesions was synergistically observed with tapasin expression and correlated positively with survival. To establish a direct link between loss of tapasin and CTL recognition in human cancer models, we targeted the tapasin gene by CRISPR/Cas9 system and generated tapasin-deficient variants of human lung as well as colon cancer cells. We induced the CTLs recognizing endogenous tumor-associated antigens (TAA), survivin or cep55, and they responded to each tapasin-proficient wild type. In contrast, both CTL lines ignored the tapasin-deficient variants despite their antigen expression. Moreover, the adoptive transfer of the cep55-specific CTL line failed to prevent tumor growth in mice bearing the tapasin-deficient variant. Loss of tapasin most likely limited antigen processing of TAAs and led to escape from TAA-specific CTL recognition. Tapasin expression is thus a key for CTL surveillance against human cancers.
authors.affiliation: Department of Pathology, Sapporo Medical University, Sapporo, Japan; Department of Respiratory Medicine and Allergology, Sapporo Medical University, Sapporo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Shionoya
authors.affiliation: Department of Pathology, Sapporo Medical University , Sapporo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kanaseki
authors.affiliation: Department of Pathology, Sapporo Medical University , Sapporo, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Miyamoto
authors.affiliation: Department of Pathology, Sapporo Medical University , Sapporo, Japan.
authors.forename: Serina
authors.initials: S
authors.lastname: Tokita
authors.affiliation: Department of Pathology, Sapporo Medical University , Sapporo, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Hongo
authors.affiliation: Department of Pathology, Sapporo Medical University , Sapporo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kikuchi
authors.affiliation: Department of Pathology, Sapporo Medical University , Sapporo, Japan.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Kochin
authors.affiliation: Department of Pathology, Sapporo Medical University, Sapporo, Japan; Research and Development Division, Medical and Biological Laboratories Company, Limited, Ina, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Pathology, Sapporo Medical University, Sapporo, Japan; Department of Respiratory Medicine and Allergology, Sapporo Medical University, Sapporo, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Horibe
authors.affiliation: Department of Pathology, Sapporo Medical University, Sapporo, Japan; Department of Respiratory Medicine and Allergology, Sapporo Medical University, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saijo
authors.affiliation: Department of Pathology, Sapporo Medical University , Sapporo, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tsukahara
authors.affiliation: Department of Pathology, Sapporo Medical University , Sapporo, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.affiliation: Department of Respiratory Medicine and Allergology, Sapporo Medical University , Sapporo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Pathology, Sapporo Medical University , Sapporo, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Pathology, Sapporo Medical University , Sapporo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
keywords: CD8+ T cells; MHC class I; colon cancer; immune evasion; lung cancer; tapasin