Advances in immunotherapy, most notably antibodies targeting the inhibitory immune receptors cytotoxic T-lymphocyte associated protein 4 (CTLA-4/CD152), programmed death protein 1 (PD-1/CD279) and programmed death-ligand 1 (PD-L1/B7H1/CD274) have become effective standard therapies in advanced malignancies including melanoma,1–4 merkel cell carcinoma5, urological cancers6–8, non-small cell lung cancer9–11, mis-match repair (MMR) deficient tumors12, and Hodgkin lymphoma with response rates ranging from 25 to 60% in the first and second line settings13,14. FDA approval has also been given for treatment for hepatocellular carcinoma, gastric cancer, triple negative breast cancer, cervical and head and neck cancers with response rates closer to 15 %15. Additionally, some clinical efficacy has been observed in ovarian cancer, mesothelioma, prostate cancer, diffuse large B cell lymphoma, follicular lymphoma, and both cutaneous and peripheral T-cell lymphoma. However, despite these successes, most patients will initially fail to respond to treatment and almost half of initial responders will develop secondary resistance to immunotherapy and progress. Moreover, many prevalent solid organ tumors remain resistant to immunotherapy including colorectal, pancreatic and hepatobiliary cancers. Therefore, new therapies are needed to increase both initial and durable response rates and to develop new mechanistic insights into pathways of immune resistance so that immunotherapy may become more widely available as a therapeutic option in common malignancies.

免疫治疗方面的进展，尤其是针对抑制性免疫受体的细胞毒性T淋巴细胞相关蛋白4（CTLA-4 / CD152），程序性死亡蛋白1（PD-1 / CD279）和程序性死亡配体1（PD-L1 / B7H1）的抗体/ CD274）已成为晚期恶性肿瘤的有效标准疗法，包括黑色素瘤，1-4默克尔细胞癌5，泌尿系统癌6-8，非小细胞肺癌9-11，错配修复（MMR）缺陷肿瘤12和霍奇金淋巴瘤有反应第一行和第二行设置中的25％到60％不等的速率13.14。FDA还批准了对肝细胞癌，胃癌，三阴性乳腺癌，宫颈癌和头颈癌的治疗，反应率接近15％15。此外，在卵巢癌，间皮瘤，前列腺癌，弥漫性大B细胞淋巴瘤，滤泡性淋巴瘤以及皮肤和外周T细胞淋巴瘤。然而，尽管取得了这些成功，但大多数患者起初对治疗均无反应，并且几乎一半的初始反应者将对免疫疗法产生次生耐药性并取得进展。此外，许多流行的实体器官肿瘤仍然对免疫疗法具有抵抗力，包括结直肠癌，胰腺癌和肝胆癌。因此，需要新的疗法来增加初始和持久应答率，并发展新的机制来了解免疫抵抗的途径，从而使免疫疗法作为常见的恶性肿瘤的治疗选择可能变得更加广泛。大多数患者最初对治疗均无反应，几乎一半的初始反应者会对免疫治疗产生抵抗力并取得进展。此外，许多流行的实体器官肿瘤仍然对免疫疗法具有抵抗力，包括结直肠癌，胰腺癌和肝胆癌。因此，需要新的疗法来增加初始和持久应答率，并发展新的机制来了解免疫抵抗的途径，从而使免疫疗法作为常见的恶性肿瘤的治疗选择可能变得更加广泛。大多数患者最初对治疗均无反应，几乎一半的初始反应者会对免疫疗法产生抗药性并取得进展。此外，许多流行的实体器官肿瘤仍然对免疫疗法具有抵抗力，包括结直肠癌，胰腺癌和肝胆癌。因此，需要新的疗法来增加初始和持久应答率，并发展新的机制来了解免疫抵抗的途径，从而使免疫疗法作为常见的恶性肿瘤的治疗选择可能变得更加广泛。胰腺癌和肝胆癌。因此，需要新的疗法来增加初始和持久应答率，并发展新的机制来了解免疫抵抗的途径，从而使免疫疗法作为常见的恶性肿瘤的治疗选择可能变得更加广泛。胰腺癌和肝胆癌。因此，需要新的疗法来增加初始和持久应答率，并发展新的机制来了解免疫抵抗的途径，从而使免疫疗法作为常见的恶性肿瘤的治疗选择可能变得更加广泛。