Oxaliplatin induces immunogenic cells death and enhances therapeutic efficacy of checkpoint inhibitor in a model of murine lung carcinoma

奥沙利铂 癌症研究 刘易斯肺癌 医学 肺癌 细胞毒性T细胞 CD80 CD86 免疫原性细胞死亡 肿瘤微环境 免疫疗法 药理学 免疫学 癌症 T细胞 免疫系统 内科学 生物 结直肠癌 CD40 转移 生物化学 肿瘤细胞 体外
作者
Fengfei Sun,Lijuan Cui,Tingting Li,Silin Chen,Song Jun-mei,Dezhi Li
出处
期刊:Journal of Receptors and Signal Transduction [Taylor & Francis]
卷期号:39 (3): 208-214 被引量:78
标识
DOI:10.1080/10799893.2019.1655050
摘要

Background: Platinum compounds are commonly used for lung cancer treatment. However, the severe side effects and relatively poor prognosis limit their therapeutic effect. Therefore, developing novel platinum derivative and treatment strategy are critical for current lung cancer therapy. Methods: Flow cytometry, HMGB1 and ATP release, and immunoblotting were performed to evaluate the Oxaliplatin-induced immunogenic cell death (ICD) in two lung carcinoma cells. Vaccination approach and subcutaneous tumor models were created to analyze the tumor regression effect of Oxaliplatin. PD-L1 mRNA and protein levels were detected in LLC (Lewis lung carcinoma). Enhanced therapeutic efficacy of LLC was assessed by co-administration Oxaliplatin and aPD-L1 in murine lung tumor model. Results: Oxaliplatin induced robust ICD in LLC cells, activated dendritic cells (DCs, CD80+CD86+) and enhanced cytotoxic T cells (CD8+) in LLC tumor tissues, which resulted in tumor regression. Co-administration of Oxaliplatin and checkpoint inhibitor, aPD-L1, could enhance the therapeutic efficacy of LLC in murine lung carcinoma. Conclusion: This study reveals Oxaliplatin can induce robust ICD in tumor tissues and suppress tumor growth by activating DCs and enhancing T-cell infiltration. Notably, the Oxaliplatin-induced ICD provides an immunogenic microenvironment, which enhances the checkpoint inhibitor therapeutic efficacy of LLC.
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