Shibayama Yuji, Tsukahara Tomohide, Emori Makoto, Murata Kenji, Mizushima Emi, Hirohashi Yoshihiko, Kanaseki Takayuki, Nakatsugawa Munehide, Kubo Terufumi, Yamashita Toshihiko, Sato Noriyuki, Torigoe Toshihiko
Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
Cancer Sci. 2017 Sep;108(9):1739-1745. doi: 10.1111/cas.13319. Epub 2017 Aug 7.
Chemotherapy has improved the prognosis of patients with sarcomas. However, it may suppress anti-tumor immunity. Recently, we reported a novel CD8 memory T cell population with a chemo-resistance property, "young memory" T (T ) cells. In this study, we investigated the proportion and function of T cells in peripheral blood of healthy donors and sarcoma patients who received chemotherapy and those who did not. The proportion of T cells was significantly decreased in patients compared with that in healthy donors. In healthy donors, anti-EBV CTLs were induced using mixed lymphocyte peptide culture, from not only T cells but also T and T cells. No CTLs directed to tumor-associated antigens were induced. In sarcoma patients who did not receive chemotherapy, in addition to anti-EBV CTLs, CTLs directed to the tumor-associated antigen PBF were induced from T , T and T cells. In sarcoma patients who received chemotherapy, EBV-specific CTLs were induced from T cells but were hardly induced from T cells. Interestingly, CTLs directed to the anti-tumor-associated antigen PBF were induced from T cells but not from the T and T cells in sarcoma patients who received chemotherapy. The findings suggest that T cells are resistant to chemotherapy and can firstly recover from the nadir. T cells might be important for immunological memory, especially in sarcoma patients receiving chemotherapy.
化疗改善了肉瘤患者的预后。然而,它可能会抑制抗肿瘤免疫力。最近,我们报道了一种具有化疗抗性的新型CD8记忆T细胞群体,即“年轻记忆”T(T)细胞。在本研究中,我们调查了健康供体以及接受化疗和未接受化疗的肉瘤患者外周血中T细胞的比例和功能。与健康供体相比,患者中T细胞的比例显著降低。在健康供体中,使用混合淋巴细胞肽培养不仅从T细胞,而且从T和T细胞诱导出抗EBV细胞毒性T淋巴细胞(CTL)。未诱导出针对肿瘤相关抗原的CTL。在未接受化疗的肉瘤患者中,除了抗EBV CTL外,还从T、T和T细胞诱导出针对肿瘤相关抗原PBF的CTL。在接受化疗的肉瘤患者中,EBV特异性CTL从T细胞诱导产生,但几乎不从T细胞诱导产生。有趣的是,在接受化疗的肉瘤患者中,针对抗肿瘤相关抗原PBF的CTL从T细胞诱导产生,而不从T和T细胞诱导产生。这些发现表明,T细胞对化疗具有抗性,并且能够首先从最低点恢复。T细胞可能对免疫记忆很重要,尤其是在接受化疗的肉瘤患者中。