免疫检查点及IL-17拮抗剂联合应用治疗非小细胞型肺癌的研究

Non-small cell lung cancer is the most common malignant lung tumor, which is the leading cause of cancer-related death worldwide, effective treatment of NSCLC remains challenging. Since anti-PD-1 antibody marking the breakthrough in immune checkpoint blocking therapy, single or combined immune therapy has been the central point in lung cancer treatment. However, because of the limitation of anti-PD-1 antibody, more effective treatment is needed. Our group has identified the role of anti-IL17 in reducing tumor number. We assume that other B7 family members have regulation roles and the blockade of these B7 family members in combination with anti-IL17 can enhance the anti-tumor effect. In the current study, NSCLC patient samples will be collected to analyze the expression of B7 family members to identify key effective molecules. Then compare the anti-tumor effect between the single treatment of key effective B7 family member blockade and its combination with anti-IL17. Finally, CCLR and IL-17 knockout mouse model will be used to study the anti-tumor effect and mechanisms of B7 family member blockade. We hypothesize that the current study will provide theoretical foundation for immune checkpoint blockade in combination with anti-IL17 in NSCLC treatment.

非小细胞型肺癌（NSCLC）是最常见的肺恶性肿瘤，也是致死率最高的癌症，目前缺乏有效的治疗方式。以免疫结合点PD-1阻断剂应用于肺癌治疗为突破，B7家族免疫结合点单独应用及与其他免疫疗法联合治疗成为关注热点。然而PD-1阻断剂仅对部分患者有效，临床上急需更有效的抗肿瘤治疗方法。本研究组前期研究发现IL-17拮抗剂可抑制小鼠肺肿瘤的形成。因此我们推测有其他B7家族免疫结合点在肺癌中起调控作用，同时免疫结合点阻断剂与IL-17拮抗剂联合作用可以增加其抗肿瘤功效。本实验拟采非小细胞型肺癌患者样本，分析B7家族分子及受体表达，鉴定出肺癌中广泛表达的B7家族分子。比较其阻断剂单独作用与和IL-17拮抗剂联合作用的抗肿瘤功效。采用小鼠肺癌模型和IL-17基因敲除小鼠，研究B7家族分子阻断剂的抗肿瘤效应及分子机制。本课题研究将免疫结合点分子单独或与IL-17拮抗剂联合作用治疗非小细胞型肺癌提供理论依据。