Dynamic changes in immune cell profile in head and neck squamous cell carcinoma: Immunomodulatory effects of chemotherapy.

Dynamic changes in immune cell profile in head and neck squamous cell carcinoma: Immunomodulatory effects of chemotherapy.
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DOI:
10.1111/cas.12976
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发表时间:
2016-08
期刊:
影响因子:
5.7
通讯作者:
Chikamatsu K
Chikamatsu K
中科院分区:
医学2区
文献类型:
--
作者:
Takahashi H;Sakakura K;Mito I;Ida S;Chikamatsu K

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肿瘤细胞已经进化出了复杂的逃离宿主免疫系统的手段。迄今为止,已经在外周血以及肿瘤内揭示了几种重要的免疫学现象。在本研究中,我们首先使用流式细胞仪研究了头颈部鳞状细胞癌(HNSCC)患者外周免疫调节细胞和CD 8 + T细胞亚群的比例和活化状态,然后评估了多西他赛,顺铂和5-氟尿嘧啶治疗如何调节外周血中的免疫细胞谱。与健康供者相比,HNSCC患者中幼稚T细胞的比例较低,效应记忆T细胞(TEM)的比例较高。此外,在晚期疾病患者中,活化的TEM细胞和效应T细胞(TEFF)的比例显著增加。HNSCC患者中调节性T细胞和CD 14 + HLA-DR −髓源性抑制细胞的比例升高。值得注意的是,治疗后,除了免疫调节细胞的短暂减少外,在CD 8 + T细胞亚群中观察到中央记忆T细胞减少和TEFF细胞增加,表明从中央记忆T细胞分化为TEFF细胞。我们的结果表明,尽管HNSCC患者的免疫抑制状态,但由CD 8 + T细胞介导的肿瘤特异性免疫应答可能被诱导和维持。此外,化疗不仅可以引发免疫调节细胞的短暂减少,还可以进一步激活CD 8 + T细胞。
Tumor cells have evolved sophisticated means of escape from the host immune system. To date, several important immunological phenomena have been revealed in peripheral blood as well as within tumors. In the present study, we first investigated the proportion and activation status of peripheral immune regulatory cells and CD8+ T‐cell subsets in patients with head and neck squamous cell carcinoma (HNSCC) using a multicolor flow cytometer, and then evaluated how therapy with docetaxel, cisplatin, and 5‐fluorouracil modulated the immune cell profile in peripheral blood. The proportion of naïve T cells was lower and that of effector memory T cells (TEM) was higher in HNSCC patients than in healthy donors. Moreover, the proportions of activated TEM cells and effector T cells (TEFF) were dramatically increased in patients with advanced stage disease. The proportion of regulatory T cells and CD14+HLA‐DR− myeloid‐derived suppressor cells was elevated in HNSCC patients. Of note, after therapy, in addition to the transient reduction in immune regulatory cells, decreases in central memory T cells and increases in TEFF cells were observed among CD8+ T‐cell subsets, suggesting differentiation from central memory T cells into TEFF cells. Our results suggested that, despite the immunosuppressive status in HNSCC patients, tumor‐specific immune responses mediated by CD8+ T cells might be induced and maintained. Moreover, chemotherapy can trigger not only a transient reduction in immune regulatory cells but also further activation of CD8+ T cells.