背景:免疫原性细胞死亡(ICD)是触发癌症患者适应性免疫反应的重要机制。损伤相关分子模式(DAMPs)是ICD检测的关键因素。化疗药物可引起ICD和DAMPs的释放。这项研究的目的是评估紫杉醇和铂类化疗方案在鳞状细胞癌(SCC)细胞系中诱导ICD的潜力。此外,我们研究了用于治疗SCC的临床相关化疗方案的免疫刺激效应.
方法:我们在用各种化学治疗剂处理后的三种SCC细胞系的上清液中筛选了差异表达的ICD标记。ICD标记包括三磷酸腺苷(ATP),钙网蛋白(CRT),AnnexinA1(ANXA1),高迁移率族蛋白B1(HMGB1),和热休克蛋白70(HSP70)。还在C57BL/6J小鼠中采用疫苗接种测定以验证我们的体外发现。最后,在SCC患者的血清样本中评估CRT和HMGB1的水平。
结果:添加化疗药物顺铂(DDP),卡铂(CBP),奈达铂(NDP),奥沙利铂(OXA)和多西他赛(DOC)增加了两种SCC细胞系中ICD标记物的释放。此外,用DDP治疗的宫颈癌细胞接种疫苗的小鼠,CBP,NDP,OXA,或DOC保持无瘤。尽管CBP在体外诱导ICD相关分子的释放,在40%的小鼠中,它不能阻止接种部位的肿瘤生长.此外,体外和体内结果显示,紫杉醇(TAX)和LBP均不诱导SCC细胞ICD。
结论:目前的研究结果表明,化疗剂可以诱导佐剂作用,导致DAMPs的细胞外释放。在这里测试的特工中,DDP,CBP,NDP,OXA和DOC具有充当ICD诱导物的能力。
BACKGROUND: Immunogenic cell death (ICD) is a crucial mechanism for triggering the adaptive immune response in cancer patients. Damage-associated molecular patterns (DAMPs) are critical factors in the detection of ICD. Chemotherapeutic drugs can cause ICD and the release of DAMPs. The aim of this study was to assess the potential for paclitaxel and platinum-based chemotherapy regimens to induce ICD in squamous cell carcinoma (SCC) cell lines. In addition, we examined the immunostimulatory effects of clinically relevant chemotherapeutic regimens utilized in the treatment of SCC.
METHODS: We screened for differentially expressed ICD markers in the supernatants of three SCC cell lines following treatment with various chemotherapeutic agents. The ICD markers included Adenosine Triphosphate (ATP),
Calreticulin (CRT), Annexin A1 (ANXA 1), High Mobility Group Protein B1 (HMGB1), and Heat Shock Protein 70 (HSP70). A vaccination assay was also employed in C57BL/6J mice to validate our in vitro findings. Lastly, the levels of CRT and HMGB1 were evaluated in Serum samples from SCC patients.
RESULTS: Addition of the chemotherapy drugs cisplatin (DDP), carboplatin (CBP), nedaplatin (NDP), oxaliplatin (OXA) and docetaxel (DOC) increased the release of ICD markers in two of the SCC cell lines. Furthermore, mice that received vaccinations with cervical cancer cells treated with DDP, CBP, NDP, OXA, or DOC remained tumor-free. Although CBP induced the release of ICD-associated molecules in vitro, it did not prevent tumor growth at the vaccination site in 40% of mice. In addition, both in vitro and in vivo results showed that paclitaxel (TAX) and LBP did not induce ICD in SCC cells.
CONCLUSIONS: The present findings suggest that chemotherapeutic agents can induce an adjuvant effect leading to the extracellular release of DAMPs. Of the agents tested here, DDP, CBP, NDP, OXA and DOC had the ability to act as inducers of ICD.