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Radiation-Enhanced Expression of CCL22 in Nasopharyngeal Carcinoma is Associated With CCR4+ CD8 T Cell Recruitment

鼻咽癌 癌症研究 医学 细胞培养 细胞毒性T细胞 中央控制室4 细胞 CD8型 放射治疗 CCL22型 分子生物学 免疫学 生物 趋化因子 免疫系统 内科学 体外 趋化因子受体 生物化学 遗传学
作者
Hanghang Li,Xiang Chen,Wenjing Zeng,Wei‐Fang Zhou,Qin Zhou,Zhan Wang,Weixiong Jiang,Bowen Xie,Lun‐Quan Sun
出处
期刊:International Journal of Radiation Oncology Biology Physics [Elsevier]
卷期号:108 (1): 126-139 被引量:19
标识
DOI:10.1016/j.ijrobp.2020.05.001
摘要

Purpose

Radiation therapy elicits profound alterations in gene expression in tumor cells. This study aims to determine the dynamic changes in the expression of immunity-associated genes in nasopharyngeal carcinoma (NPC) cells upon radiation therapy.

Methods and Materials

The study was performed using NPC patient-derived tumor xenograft tumors, cell lines, CCR4+ CD8 T cells sorted from peripheral blood mononuclear cells of healthy volunteers, and TCGA-derived bulk RNA-seq or single-cell RNA-seq (scRNA-seq) data sets. Patient-derived tumor xenograft tumors or cell lines were irradiated and collected for bulk RNA sequencing or for CCL22 expression and release detection. Malignant phenotypes and radiosensitivity were assessed in cells with or without overexpression of CCL22 or recombinant CCL22 treatment in the presence or absence of irradiation. TCGA data sets were used for uncovering CCR4 status in subtypes of T cells. CCL22 in supernatants, cell lysates, or serum samples was measured with enzyme-linked immunosorbent assay.

Results

CCL22 was significantly increased in the irradiated patient-derived tumor xenograft tumors, the supernatants and cell lysates collected from irradiated NPC cell lines, and the serum of patients who received radiation therapy. No alterations of malignant phenotypes were found in tumor cells with CCL22 overexpression or recombinant CCL22 treatment. Kaplan-Meier analysis revealed that CCL22 or its receptor CCR4 positively correlated with cytotoxic T lymphocyte signatures, and high expression of CCL22 or CCR4 was associated with better prognosis for patients with NPC. scRNA-seq data set–based analysis demonstrated that CCR4 was expressed in multiple subtypes of T cells, including effector CD8 T cells. Chemotaxis assay indicated that CCR4+ CD8 T cells could be recruited by CCL22 treatment.

Conclusion

The radiation-enhanced release of CCL22 from NPC cells promotes migration of CCR4 + effector CD8 T cells, which might partially be associated with radiation therapy–mediated antitumor immunity.
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