Tumor-expressed immune checkpoint B7x-mediated resistance to anti-CTLA-4 therapy.

肿瘤表达的免疫检查点B7 x介导的对 抗CTLA-4治疗 CTLA-4和PD-1/PD-L1的免疫检查点阻断已经进展 癌症患者的治疗。然而，最大的挑战之一是， 大多数癌症患者对这些治疗没有反应。基于我们 新的结果，我们提出的修订研究的中心假设是， 肿瘤表达的免疫检查点B7 x诱导对抗CTLA-4的抗性 抗B7 x和抗CTLA-4联合治疗导致 协同治疗功效并克服抗CTLA-4抗性 疗法在我们已发表的临床和基础研究的指导下， 初步数据，我们将追求两个具体目标：1）剖析机制 潜在的肿瘤表达的B7 x介导的对抗CTLA-4治疗的抗性; 和2）开发抗B7 x和抗CTLA-4的新型组合疗法， 克服阻力。我们已经为此开发了许多新颖的工具 项目该项目的成果将揭示新的机制， 肿瘤表达的B7 x介导的抗CTLA-4治疗抗性， 开发出克服耐药性的新的免疫疗法。

Tumor-expressed immune checkpoint B7x-mediated resistance to anti-CTLA-4 therapy Immune checkpoint blockade of CTLA-4 and PD-1/PD-L1 have advanced the treatment of cancer patients. However, one of the biggest challenges is that the majority of cancer patients do not respond to these treatments. Based on our new results, our central hypothesis of this proposed revision research is that tumor-expressed immune checkpoint B7x induces resistance to anti-CTLA-4 therapy and that combination treatment of anti-B7x and anti-CTLA-4 leads to synergistic therapeutic efficacy and overcomes the resistance to anti-CTLA-4 therapy. Guided by our published clinical and basic research, and our strong preliminary data, we will pursue two specific aims: 1) Dissect the mechanisms underlying tumor-expressed B7x mediated resistance to anti-CTLA-4 therapy; and 2) Develop novel combination therapies of anti-B7x and anti-CTLA-4 to overcome the resistance. We have generated a number of novel tools for this project. The outcomes of this project will reveal new mechanisms underlying tumor-expressed B7x-mediated resistance to anti-CTLA-4 therapy and will develop into new immunotherapies overcoming the resistance.