Loss of tapasin in human lung and colon cancer cells and escape from tumor-associated antigen-specific CTL recognition.

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Loss of tapasin in human lung and colon cancer cells and escape from tumor-associated antigen-specific CTL recognition.

Oncoimmunology. 2017;6(2):e1274476

Authors: Shionoya Y, Kanaseki T, Miyamoto S, Tokita S, Hongo A, Kikuchi Y, Kochin V, Watanabe K, Horibe R, Saijo H, Tsukahara T, Hirohashi Y, Takahashi H, Sato N, Torigoe T

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.

PMID: 28344889 [PubMed - in process]

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