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

机译:头颈鳞状细胞癌免疫细胞谱的动态变化:化疗的免疫调节作用

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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 naive 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.
机译:肿瘤细胞已经从宿主免疫系统中进化了复杂的逃逸方法。迄今为止,在外周血以及肿瘤内揭示了几种重要的免疫现象。在本研究中,我们首先研究了使用多色流式细胞仪的头部和颈部鳞状细胞癌(HNSCC)患者的外周免疫调节细胞和CD8(+)T细胞亚群的比例和激活状态,然后评估如何治疗用多西紫杉醇,顺铂和5-氟尿嘧啶调节外周血中的免疫细胞谱。幼稚T细胞的比例较低,HNSCC患者的效应记忆T细胞(TEM)的比例较高,而不是健康的供体。此外,在晚期阶段疾病的患者中,活化TEM细胞和效应T细胞(TEFF)的比例显着增加。调节性T细胞和CD14(+)HLA-DR-髓样衍生抑制细胞的比例在HNSCC患者中升高。备注,在治疗后,除了瞬态降低免疫调节细胞之外,中央记忆T细胞的降低以及在CD8(+)T细胞亚群中观察到中央记忆T细胞的增加,表明将从中央记忆T细胞分化为TEFF细胞。我们的研究结果表明,尽管HNSCC患者的免疫抑制状态,但可诱导和维持由CD8(+)T细胞介导的肿瘤特异性免疫应答。此外,化疗不仅可以触发免疫调节细胞的瞬态还原,还可以进一步激活CD8(+)T细胞。

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