Ionizing Radiation Reduces Head and Neck Squamous Cell Carcinoma Cell Viability and Is Associated with Predictive Tumor-Specific T Cell Responses.
Ionizing Radiation Reduces Head and Neck Squamous Cell Carcinoma Cell Viability and Is Associated with Predictive Tumor-Specific T Cell Responses.
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电离辐射可降低头颈鳞状细胞癌细胞活力，并与预测性肿瘤特异性T细胞反应有关。
作者：
当今晚期头颈鳞状细胞癌（HNSCC）的标准治疗是侵入性手术切除。放射联合治疗因其减少这些癌症中常见的肿瘤复发的能力而受到广泛关注。我们研究的目的是研究肿瘤靶向放射治疗产生能够引发宿主免疫反应途径的肿瘤抗原的能力。使用将肿瘤细胞注射到具有免疫能力的小鼠体内的 HNSCC 小鼠模型，我们确定与其他肿瘤抗原制备方法相比，通过肿瘤细胞照射产生的抗原可诱导有效的免疫反应。与传统的抗 CD3 和 CD28 抗体相比，这种反应也表现出相当的敏感性，但对 T 细胞激活具有更高的特异性。该信息可用于预测患者对放射和免疫治疗的反应。头颈鳞状细胞癌 (HNSCC) 常见且致命，需要改进策略来预测治疗反应。电离辐射 (IR) 已被证明可以改善 HNSCC 的预后，但其对免疫反应的影响尚不清楚。我们确定了 IR 对离体 T 细胞免疫反应的影响。将人和小鼠 HNSCC 细胞暴露于 20 至 200 Gy 的红外线下，以确定细胞活力和刺激 T 细胞特异性反应的能力。用源自经 200 Gy IR、紫外线 (UV) 暴露或冷冻/解冻循环处理处理的 LY2 或 MOC2 细胞的肿瘤抗原重新刺激 LY2 和 MOC2 荷瘤或非荷瘤小鼠的淋巴结细胞。将 T 细胞增殖和细胞因子产生与用板结合的 CD3 和 CD28 抗体再刺激的 T 细胞进行比较。人类和小鼠 HNSCC 细胞对电离辐射的反应活性降低，且呈剂量依赖性，并诱导 T 细胞趋化细胞因子的表达。 IR 处理的 LY2 和 MOC2 细胞衍生的肿瘤抗原诱导荷瘤小鼠淋巴结细胞的更大增殖，并诱导独特的 T 细胞细胞因子表达谱。我们的结果表明，IR 诱导有效的肿瘤免疫反应，并且 IR 产生的肿瘤抗原可以在离体 T 细胞再刺激测定中作为 HNSCC 抗肿瘤免疫反应的指标。
Today’s standard of treatment for advanced head and neck squamous cell carcinoma (HNSCC) is invasive surgical resection. Radiation co-therapy has received a great deal of attention for its ability to reduce tumor recurrence, common in these cancers. The aim of our study was to investigate the ability of tumor-targeted radiation therapy to generate tumor antigens capable of eliciting host immune response pathways. Using a murine model of HNSCC with tumor cells injected into immune-competent mice, we determined that antigens generated by the irradiation of tumor cells induced potent immune responses compared to other methods for tumor antigen preparations. This response was also found to display comparable sensitivity, but greater specificity for T cell activation compared to conventional anti-CD3 and CD28 antibodies. This information may be utilized to predict patient responses to radiation and immune therapy. Head and neck squamous cell carcinoma (HNSCC) is common and deadly, and there is a need for improved strategies to predict treatment responses. Ionizing radiation (IR) has been demonstrated to improve HNSCC outcomes, but its effects on immune responses are not well characterized. We determined the impact of IR on T cell immune responses ex vivo. Human and mouse HNSCC cells were exposed to IR ranging from 20 to 200 Gy to determine cell viability and the ability to stimulate T-cell-specific responses. Lymph node cells of LY2 and MOC2 tumor-bearing or non-tumor-bearing mice were re-stimulated with a tumor antigen derived from LY2 or MOC2 cells treated with 200 Gy IR, ultraviolet (UV) exposure, or freeze/thaw cycle treatments. T cell proliferation and cytokine production were compared to T cells restimulated with plate-bound CD3 and CD28 antibodies. Human and mouse HNSCC cells showed reduced viability in response to ionizing radiation in a dose-dependent manner, and induced expression of T cell chemotactic cytokines. Tumor antigens derived from IR-treated LY2 and MOC2 cells induced greater proliferation of lymph node cells from tumor-bearing mice and induced unique T cell cytokine expression profiles. Our results demonstrate that IR induces potent tumoral immune responses, and IR-generated tumor antigens can potentially serve as an indicator of antitumor immune responses to HNSCC in ex vivo T cell restimulation assays.
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DOI：
10.1126/science.aaf7532
发表时间：
2016-11-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hu B;Jin C;Li HB;Tong J;Ouyang X;Cetinbas NM;Zhu S;Strowig T;Lam FC;Zhao C;Henao-Mejia J;Yilmaz O;Fitzgerald KA;Eisenbarth SC;Elinav E;Flavell RA
通讯作者：
Flavell RA
影响因子：
5.6
作者：
Mirzayans R;Andrais B;Scott A;Wang YW;Murray D
通讯作者：
Murray D
影响因子：
3.8
作者：
Lalla, R. V.;Treister, N.;Brennan, M. T.
通讯作者：
Brennan, M. T.
影响因子：
3
作者：
Feller G;Khammissa RAG;Nemutandani MS;Feller L
通讯作者：
Feller L
DOI：
10.1159/000328340
发表时间：
2011-01-01
期刊：
ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES
影响因子：
--
作者：
Camisasca, Danielle Resende;Nunes Costa Silami, Marcos Antonio;Chaves Lourenco, Simone de Queiroz
通讯作者：
Chaves Lourenco, Simone de Queiroz