Background/Objectives: Radiotherapy (RT) is a mainstay of clinical cancer therapy that causes broad immune responses. The complement system is a pivotal effector mechanism in the innate immune response, but the impact of RT is less well understood. This study investigates the interaction between RT and the complement system as a possible approach to improve immune responses in cancer treatment.Methods: Human solid cancer (lung, prostate, liver, breast cancer), lymphoma, and leukemia cells were irradiated using X-rays and treated with polyclonal antibodies or anti-CD20 monoclonal antibodies, respectively. Chromium release assay was applied to measure cell lysis after radiation with or without complement-activating antibody treatment. The expression of membrane-bound complement regulatory proteins (mCRPs; CD46, CD55, CD59), which confer resistance against complement activation, CD20 expression, apoptosis, and radiation-induced DNA double-strand breaks (γH2AX), was measured by flow cytometry. The radiosensitivity of tumor cells was assessed by colony-forming assay.Results: We demonstrate that RT profoundly impacts complement function by upregulating the expression of membrane-bound complement regulatory proteins (mCRPs) on tumor cells in a dose- and time-dependent manner. Impaired complement-mediated tumor cell lysis could thus potentially contribute to radiotherapeutic resistance. We also observed RT-induced upregulation of CD20 expression on lymphoma and leukemic cells. Notably, complement activation prior to RT proved more effective in inducing RT-dependent early apoptosis compared to post-irradiation treatment. While complement modulation does not significantly alter RT-induced DNA-damage repair mechanisms or intrinsic radiosensitivity in cancer cells, our results suggest that combining RT with complement-based anti-cancer therapy may enhance complement-dependent cytotoxicity (CDC) and apoptosis in tumor cells.Conclusions: This study sheds light on the complex interplay between RT and the complement system, offering insights into potential novel combinatorial therapeutic strategies and a potential sequential structure for certain tumor types.
背景/目的：放射治疗（RT）是临床癌症治疗的主要手段，能引发广泛的免疫反应。补体系统是先天免疫应答中的关键效应机制，但RT对其影响尚不明确。本研究探讨RT与补体系统之间的相互作用，以探索改善癌症治疗中免疫应答的可能途径。 方法：采用X射线照射人实体瘤（肺癌、前列腺癌、肝癌、乳腺癌）、淋巴瘤及白血病细胞，并分别使用多克隆抗体或抗CD20单克隆抗体处理。通过铬释放实验检测放疗联合或不联合补体激活抗体处理后的细胞裂解情况。采用流式细胞术检测膜结合补体调节蛋白（mCRPs；CD46、CD55、CD59，可抵抗补体激活）、CD20表达、细胞凋亡及辐射诱导的DNA双链断裂（γH2AX）。通过克隆形成实验评估肿瘤细胞的放射敏感性。 结果：研究发现RT以剂量和时间依赖性方式显著上调肿瘤细胞膜结合补体调节蛋白（mCRPs）的表达，从而影响补体功能。补体介导的肿瘤细胞裂解受损可能因此导致放射治疗抵抗。同时观察到RT诱导淋巴瘤和白血病细胞CD20表达上调。值得注意的是，与放疗后处理相比，放疗前激活补体能更有效地诱导RT依赖性早期凋亡。虽然补体调节未显著改变RT诱导的DNA损伤修复机制或肿瘤细胞的内在放射敏感性，但结果表明RT联合基于补体的抗癌治疗可能增强肿瘤细胞的补体依赖性细胞毒性（CDC）和凋亡。 结论：本研究揭示了RT与补体系统之间复杂的相互作用，为开发潜在的新型联合治疗策略及针对特定肿瘤类型的序贯治疗方案提供了新见解。
肿瘤(癌症)患者之家