Challenges and Opportunities for Pancreatic Cancer Immunotherapy.

Challenges and Opportunities for Pancreatic Cancer Immunotherapy.
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DOI:
10.1016/j.ccell.2020.08.004
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发表时间:
2020-12-14
期刊:
影响因子:
50.3
通讯作者:
O'Hara MH
O'Hara MH
中科院分区:
医学1区
文献类型:
--
作者:
Bear AS;Vonderheide RH;O'Hara MH

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胰腺导管腺癌(PDA)是免疫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图谱从肿瘤发生的最早阶段就促进免疫抑制,从而破坏适应性T细胞免疫。到目前为止,单药免疫调节剂在临床上已被证明无效,可能需要针对免疫治疗抗性机制的多模式疗法。在此,我们综述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细胞效应功能,以及(3)中和肿瘤微环境中的免疫抑制成分,这些策略可能合理组合以解开胰腺导管腺癌和其他肿瘤中的免疫抗性网络。
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. Herein, 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.
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