Shanghai High School International Division, Shanghai, 200231, China.
Stud Health Technol Inform. 2023 Nov 23;308:341-350. doi: 10.3233/SHTI230858.
Breast cancer is the most commonly diagnosed cancer with over 2.3 million new cases diagnosed and 685,000 deaths worldwide in 2020. Triple-negative breast cancer (TNBC), which is characterized by high invasiveness, high metastatic potential, poor prognosis, and proneness to relapse, accounts for approximately 15-20% of all cancer types. Despite the numerous treatments available, it is reported that TNBC patients develop resistance to chemotherapeutic drugs frequently and have a relatively low response rate to immunotherapy due to insufficient T-lymphocyte infiltration. In this study, human breast cancer cells MDA-MB-231 are treated with increasing concentrations and treatment durations of Oxaliplatin to investigate the anti-cancer potential of Oxaliplatin. A xenograft assay with MDA-MB-231 is further pursued to test the efficacy of the combination treatment of Oxaliplatin and Pembrolizumab, a monoclonal anti-PD-1 antibody. For the xenograft assay, tumor growth is measured after receiving Oxaliplatin followed by Pembrolizumab. Immunogenetic cell death (ICD) in vitro is measured by flow cytometry of calreticulin (CRT) and Western blot of high mobility group protein B1 (HMGB1) in supernatant; cytotoxic T-lymphocyte infiltration is measured in the xenograft model via flow cytometry using T-cell markers from cells retrieved from the tumor mass; tumor growth is measured using the digital caliper. The result of this study provides insight into the anti-cancer potential of Oxaliplatin and Pembrolizumab combination treatment in TNBC, providing a reference for future studies of combining chemotherapy and immunotherapy in treating breast cancer.
乳腺癌是最常见的癌症类型，2020 年全球新发病例超过 230 万例，死亡病例 68.5 万例。三阴性乳腺癌（TNBC）具有侵袭性高、转移潜能高、预后差、易复发等特点，约占所有癌症类型的 15-20%。尽管有许多治疗方法可用，但据报道，TNBC 患者经常对化疗药物产生耐药性，并且由于 T 淋巴细胞浸润不足，对免疫疗法的反应率相对较低。在这项研究中，用不同浓度和不同处理时间的奥沙利铂处理人乳腺癌细胞 MDA-MB-231，以研究奥沙利铂的抗癌潜力。进一步进行 MDA-MB-231 的异种移植实验，以测试奥沙利铂与 Pembrolizumab（一种单克隆抗 PD-1 抗体）联合治疗的疗效。对于异种移植实验，在接受奥沙利铂后再接受 Pembrolizumab，测量肿瘤生长情况。通过流式细胞术检测钙网蛋白（CRT）和上清液中高迁移率族蛋白 B1（HMGB1）的 Western blot 测量体外免疫原性细胞死亡（ICD）；通过从肿瘤块中取出的细胞的 T 细胞标志物在异种移植模型中测量细胞毒性 T 淋巴细胞浸润；使用数字卡尺测量肿瘤生长情况。这项研究的结果提供了奥沙利铂和 Pembrolizumab 联合治疗在 TNBC 中的抗癌潜力的见解，为未来在治疗乳腺癌中结合化疗和免疫疗法的研究提供了参考。
