Tumor Cells Surviving Exposure to Proton or Photon Radiation Share a Common Immunogenic Modulation Signature, Rendering Them More Sensitive to T Cell-Mediated Killing
Tumor Cells Surviving Exposure to Proton or Photon Radiation Share a Common Immunogenic Modulation Signature, Rendering Them More Sensitive to T Cell-Mediated Killing
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DOI：
10.1016/j.ijrobp.2016.02.022
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发表时间：
2016-05-01
影响因子：
7
通讯作者：
Hodge, James W.
中科院分区：
文献类型：
--
作者：
Gameiro, Sofia R.;Malamas, Anthony S.;Hodge, James W.
目的：为将诱导肿瘤抗原特异性T细胞的免疫治疗与质子放射治疗相结合以利用这些T细胞的活性提供基础。使用经常用质子辐射治疗的肿瘤细胞系，如前列腺、乳腺、肺和脉络膜，我们通过流式细胞术检测了质子辐射对肿瘤细胞的存活率和免疫原性调节的诱导的影响，结果：这些研究首次表明：（1）质子和光子辐射诱导与免疫识别相关的表面分子的上调相当（组织相容性白细胞抗原、细胞间粘附分子1和肿瘤相关抗原癌胚抗原和粘蛋白1）;（2）质子辐射介导的钙网蛋白细胞表面表达，增加了对细胞毒性T淋巴细胞杀伤肿瘤细胞的敏感性;（3）对质子辐射的直接细胞溶解活性有抗性的癌症干细胞，在辐射后以类似于非癌症干细胞的方式上调钙网蛋白。这些发现为质子放射联合免疫治疗提供了理论依据，包括单独放射治疗失败或治疗选择有限的患者。爱思唯尔公司出版。
Purpose: To provide the foundation for combining immunotherapy to induce tumor antigen-specific T cells with proton radiation therapy to exploit the activity of those T cells.Methods and Materials: Using cell lines of tumors frequently treated with proton radiation, such as prostate, breast, lung, and chordoma, we examined the effect of proton radiation on the viability and induction of immunogenic modulation in tumor cells by flow cytometric and immunofluorescent analysis of surface phenotype and the functional immune consequences.Results: These studies show for the first time that (1) proton and photon radiation induced comparable up-regulation of surface molecules involved in immune recognition (histocompatibility leukocyte antigen, intercellular adhesion molecule 1, and the tumor-associated antigens carcinoembryonic antigen and mucin 1); (2) proton radiation mediated calreticulin cell-surface expression, increasing sensitivity to cytotoxic T-lymphocyte killing of tumor cells; and (3) cancer stem cells, which are resistant to the direct cytolytic activity of proton radiation, nonetheless up-regulated calreticulin after radiation in a manner similar to non-cancer stem cells.Conclusions: These findings offer a rationale for the use of proton radiation in combination with immunotherapy, including for patients who have failed radiation therapy alone or have limited treatment options. Published by Elsevier Inc.