Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma
Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma
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DOI：
10.4049/jimmunol.169.5.2756
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发表时间：
2002-09-01
影响因子：
4.4
通讯作者：
Linehan, DC
中科院分区：
文献类型：
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作者：
Liyanage, UK;Moore, TT;Linehan, DC
通过抑制自身反应性T细胞来预防自身免疫性疾病的调节性T细胞（T1，g）也可以抑制针对癌症的免疫应答。在小鼠中，通过Ab治疗耗尽T-reg导致更有效的肿瘤排斥。T-reg介导的抗肿瘤免疫应答抑制可能部分解释了基于疫苗的人类癌症免疫治疗的临床应答差。在这项研究中，我们测量了65例胰腺癌或乳腺癌患者的PBL、肿瘤浸润淋巴细胞和区域淋巴结淋巴细胞中共表达CD 4和CD 25的T-reg的患病率。在乳腺癌患者（n = 35）、胰腺癌患者（n = 30）和正常献血员（n = 35）中，T-reg的患病率分别为总CD 4（+）细胞的16.6%（SE 1.22）、13.2%（SE 1.13）和8.6%（SE 0.71）。乳腺癌和胰腺癌患者的T-reg阳性率均显著高于正常人（P <0.01）。在肿瘤浸润淋巴细胞和淋巴结淋巴细胞中，T-reg阳性率分别为20.2%（SE 3.93）和20.1%（SE 4.3）。Treg组成型共表达CTLA-4和CD 45 RO标记物，并分泌TGF-β和IL-10，但不分泌IFN-γ。当与活化的CD 8（+）细胞或CD 4（+）25（-）细胞共培养时，Treg有效地抑制它们的增殖和IFN-γ的分泌。我们的结论是，T-reg的患病率增加，在外周血中，以及在浸润性乳腺癌或胰腺癌患者的肿瘤微环境。这些T-reg可以减轻针对癌症的免疫应答，并且可以部分解释针对肿瘤Ag的免疫应答差。
Regulatory T cells (T,,g) that prevent autoimmune diseases by suppression of self-reactive T cells may also suppress the immune response against cancer. In mice, depletion of T-reg by Ab therapy leads to more efficient tumor rejection. T-reg-mediated suppression of antitumor immune responses may partly explain the poor clinical response to vaccine-based immunotherapy for human cancer. In this study, we measured the prevalence of T-reg that coexpress CD4 and CD25 in the PBLs, tumor-infiltrating lymphocytes, and regional lymph node lymphocytes from 65 patients with either pancreas or breast cancer. In breast cancer patients (n = 35), pancreas cancer patients (n = 30), and normal donors (n = 35), the prevalence of T-reg were 16.6% (SE 1.22), 13.2% (SE 1.13), and 8.6% (SE 0.71) of the total CD4(+) cells, respectively. The prevalence of T-reg, were significantly higher in breast cancer patients (p < 0.01) and pancreas cancer patients (p < 0.01) when compared with normal donors. In tumor-infiltrating lymphocytes and lymph node lymphocytes, the T-reg prevalence were 20.2% (SE 3.93) and 20.1% (SE 4.3), respectively. Treg constitutively coexpressed CTLA-4 and CD45RO markers, and secreted TGF-beta and IL-10 but did not secrete IFN-gamma. When cocultured with activated CD8(+) cells or CD4(+)25(-) cells, Treg potently suppressed their proliferation and secretion of IFN-gamma. We conclude that the prevalence of T-reg is increased in the peripheral blood as well as in the tumor microenvironment of patients with invasive breast or pancreas cancers. These T-reg may mitigate the immune response against cancer, and may partly explain the poor immune response against tumor Ags.