Pancreatic ductal adenocarcinoma (PDA) is among the most immune-resistant tumor types. Its unique genomic landscape shaped by oncogenic drivers promotes immune suppression from the earliest stages of tumor inception to subvert adaptive T cell immunity. Single-agent immune modulators have thus far proven clinically ineffective, and multi-modal therapies targeting mechanisms of immunotherapy resistance are likely needed. Here, we review novel immunotherapy strategies currently under investigation to (1) confer antigen specificity, (2) enhance T cell effector function, and (3) neutralize immunosuppressive elements within the tumor microenvironment that may be rationally combined to untangle the web of immune resistance in PDA and other tumors.

胰腺导管腺癌 (PDA) 是免疫抵抗性最强的肿瘤类型之一。其由致癌驱动因素塑造的独特基因组景观从肿瘤发生的最早阶段促进免疫抑制，以颠覆适应性 T 细胞免疫。迄今为止，单药免疫调节剂已被证明在临床上无效，并且可能需要针对免疫疗法耐药机制的多模式疗法。在这里，我们回顾了目前正在研究的新型免疫治疗策略，以 (1) 赋予抗原特异性，(2) 增强 T 细胞效应器功能，以及 (3) 中和肿瘤微环境中的免疫抑制元素，这些元素可以合理组合以解开免疫抵抗网络在 PDA 和其他肿瘤中。