RRC ID 72827
著者 Sawada M, Goto K, Morimoto-Okazawa A, Haruna M, Yamamoto K, Yamamoto Y, Nakagawa S, Hiramatsu K, Matsuzaki S, Kobayashi E, Kawashima A, Hirata M, Iwahori K, Kimura T, Ueda Y, Kimura T, Wada H.
タイトル PD-1+ Tim3+ tumor-infiltrating CD8 T cells sustain the potential for IFN-γ production, but lose cytotoxic activity in ovarian cancer.
ジャーナル Int Immunol
Abstract Persistent exposure to tumor antigens results in exhausted tumor-infiltrating T cells (TILs) that express the immune checkpoint molecules, PD-1 and Tim3, and lack anti-tumor immunity. To examine the exhausted status of TILs in ovarian cancer, the potential for cytokine production, proliferation and cytotoxicity by purified PD-1+ Tim3+ CD8 TILs was assessed. The production of IFN-γ and TNF-α by PD-1+ Tim3+ CD8 TILs remained the same in an intracellular cytokine staining assay and was higher in a cytokine catch assay than that by PD-1- Tim3- and PD-1+ Tim3- CD8 TILs. %Ki67+ was higher in PD-1+ Tim3+ CD8 TILs than in PD-1- Tim3- CD8 TILs. However, patients with high PD-1+ Tim3+ CD8 TILs had a poor prognosis. The potential for cytotoxicity was then examined. %Perforin+ and %granzyme B+ were lower in PD-1+ Tim3+ CD8 TILs than in PD-1- Tim3- and PD-1+ Tim3- CD8 TILs. To observe the potential for direct cytotoxicity by T cells, a target cell line expressing membrane-bound anti-CD3scFv was newly established and a cytotoxic assay targeting these cells was performed. The cytotoxicity of PD-1+ Tim3+ CD8 TILs was significantly lower than that of PD-1- Tim3- and PD-1+ Tim3- CD8 TILs. Even though PD-1+ Tim3+ CD8 TILs in ovarian cancer showed a sustained potential for cytokine production and proliferation, cytotoxicity was markedly impaired, which may contribute to the poor prognosis of patients with ovarian cancer. Among the impaired functions of exhausted TILs, cytotoxicity may be an essential target for cancer immunotherapy.
巻・号 32(6)
ページ 397-405
公開日 2020-5-30
DOI 10.1093/intimm/dxaa010
PII 5721204
PMID 32009163
MeSH Adult Aged Aged, 80 and over CD8-Positive T-Lymphocytes / immunology* Cell Proliferation Female Hepatitis A Virus Cellular Receptor 2 / deficiency Hepatitis A Virus Cellular Receptor 2 / immunology* Humans Immunotherapy Interferon-gamma / biosynthesis* Interferon-gamma / immunology Lymphocytes, Tumor-Infiltrating / immunology* Middle Aged Ovarian Neoplasms / diagnosis Ovarian Neoplasms / immunology* Ovarian Neoplasms / metabolism Ovarian Neoplasms / therapy Programmed Cell Death 1 Receptor / deficiency Programmed Cell Death 1 Receptor / immunology*
IF 3.519
リソース情報
ヒト・動物細胞 BALL-1(RCB0256)