Blockade of TGF-β signaling: a potential target for cancer immunotherapy?
Ungefroren (2019) Blockade of TGF-β signaling: a potential target for cancer immunotherapy? Expert Opin Ther Targets (IF: 5.8) 23(8) 679-693Abstract
Introduction: Malignant tumors often escape surveillance and eventual destruction by the host immune system through a variety of strategies including production of transforming growth factor (TGF)-β. Because of its generally immunosuppressive role, TGF-β has emerged as a promising therapeutic target in cancer immunotherapy. Areas covered: This article looks at specific mechanisms of how TGF-β controls the function of various immune cell subsets in the tumor microenvironment and focusses on T-cells. Various inhibition tools of TGF-β signaling and potential targets of therapeutic intervention are assessed along with the recent progress in combining TGF-β blockade and immune-mediated therapies. To round off the article, a summary of results from clinical trials is provided in which TGF-β blockade has shown therapeutic benefit for patients. Expert opinion: Data from preclinical models have shown that blocking TGF-β signaling can overcome resistance mechanisms and in combination with immune-checkpoint therapies, can yield additive or synergistic anti-tumor responses. The future of immunooncology will therefore be based on combination trials. Since response rates may critically depend on both cancer type and stage, selection of only those patients who can benefit from combinatorial immunotherapy regimens is of utmost importance.
简介：恶性肿瘤通常通过包括转化生长因子（TGF）-β产生在内的多种策略逃避宿主免疫系统的监视和最终破坏。由于其通常的免疫抑制作用，TGF-β已成为癌症免疫疗法中有希望的治疗靶标。涵盖的领域：本文探讨了TGF-β如何控制肿瘤微环境中各种免疫细胞亚群的功能并关注T细胞的具体机制。评估了TGF-β信号传导的各种抑制工具和治疗干预的潜在靶标，以及结合TGF-β阻断和免疫介导的治疗的最新进展。为了完善该文章，提供了临床试验结果的总结，其中TGF-β阻断已经为患者显示出治疗益处。专家意见：来自临床前模型的数据显示阻断TGF-β信号传导可克服抗性机制，并与免疫检查点疗法相结合，可产生加性或协同抗肿瘤反应。因此，免疫生态学的未来将基于组合试验。由于应答率可能关键取决于癌症类型和阶段，因此仅选择那些可以从组合免疫治疗方案中受益的患者是至关重要的。
Links
http://www.ncbi.nlm.nih.gov/pubmed/31232607http://dx.doi.org/10.1080/14728222.2019.1636034
