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顺铂为基础的放化疗降低端粒酶特异性 CD4 TH1 反应,但增加外周血免疫抑制细胞。

Cisplatin-based chemoradiation decreases telomerase-specific CD4 TH1 response but increases immune suppressive cells in peripheral blood.

机构信息

Department of Radiation Oncology, University Hospital of Besançon, 25000, Besançon, France.

INSERM, EFS BFC, UMR1098, RIGHT, Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, University of Bourgogne Franche-Comté, 25000, Besançon, France.

出版信息

BMC Immunol. 2021 Jun 18;22(1):38. doi: 10.1186/s12865-021-00429-5.

DOI:10.1186/s12865-021-00429-5
PMID:34144673
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8212531/
Abstract

BACKGROUND

The synergistic effect of chemoradiation (CRT) has been previously demonstrated in several cancer types. Here, we investigated the systemic immune effects of CRT in patients with lung or head and neck cancer.

MATERIALS AND METHODS

Peripheral blood mononuclear cells were collected at baseline and 1 month after treatment from blood samples of 29 patients treated with cisplatin-based chemoradiotherapy for lung or head and neck cancer. Circulating anti-tumor Th1 response was assessed by the ELISpot assay using a mixture of human leucocyte antigen (HLA) class II restricted peptides derived from telomerase (TERT). Phenotyping of circulating immunosuppressive cells (Treg and MDSC) was performed by flow cytometry.

RESULTS

A significant increase of circulating Treg was observed in 60% of patients after CRT The mean rate of Treg was 3.1% versus 4.9% at baseline and after CRT respectively, p = 0.0015). However, there was a no significant increase of MDSC rate after CRT. In contrast, a decrease of tumor-specific Th1 response was documented in 7 out of 10 evaluated patients. We found high frequency of pre-existing tumor-specific Th1 response among patients with objective response after CRT compared to non-responders.

CONCLUSION

Cisplatin-based CRT promotes expansion of Treg and decrease of circulating anti-tumor Th1 response in peripheral blood. The balance towards a sustained specific anti-tumor T-cell response appears to be associated with response to CRT.

摘要

背景

化学放疗(CRT)的协同效应已在多种癌症类型中得到证实。在这里,我们研究了 CRT 对肺癌或头颈部癌症患者的全身免疫效应。

材料与方法

从 29 例接受顺铂为基础的放化疗的肺癌或头颈部癌症患者的治疗前后的血液样本中收集外周血单核细胞。使用来自端粒酶(TERT)的 HLA Ⅱ类限制性肽混合物,通过 ELISpot 测定评估循环抗肿瘤 Th1 反应。通过流式细胞术对循环免疫抑制细胞(Treg 和 MDSC)进行表型分析。

结果

在 CRT 后,60%的患者观察到循环 Treg 显著增加。Treg 的平均比率分别为 3.1%和 4.9%,p=0.0015)。然而,CRT 后 MDSC 比率没有显著增加。相比之下,在 10 例评估的患者中有 7 例记录到肿瘤特异性 Th1 反应下降。我们发现,在 CRT 后有客观反应的患者中,存在高频率的预先存在的肿瘤特异性 Th1 反应,而无反应者则没有。

结论

顺铂为基础的 CRT 促进 Treg 的扩增和外周血中循环抗肿瘤 Th1 反应的下降。平衡向持续的特异性抗肿瘤 T 细胞反应似乎与 CRT 反应相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c3/8212531/5c0442d34851/12865_2021_429_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c3/8212531/bbcec6f5e36e/12865_2021_429_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c3/8212531/5d9e1b86a7be/12865_2021_429_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c3/8212531/5c0442d34851/12865_2021_429_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c3/8212531/bbcec6f5e36e/12865_2021_429_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c3/8212531/5d9e1b86a7be/12865_2021_429_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25c3/8212531/5c0442d34851/12865_2021_429_Fig3_HTML.jpg

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