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癌症中TIM-3通路的失调与靶向治疗

TIM-3 pathway dysregulation and targeting in cancer.

作者信息

Zeidan Amer M, Komrokji Rami S, Brunner Andrew M

机构信息

Department of Internal Medicine, Section of Hematology, Yale University School of Medicine, New Haven, CT, USA.

Malignant Hematology Department, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

出版信息

Expert Rev Anticancer Ther. 2021 May;21(5):523-534. doi: 10.1080/14737140.2021.1865814. Epub 2021 Jan 19.

Abstract

INTRODUCTION

Dysfunction of the immune system is a hallmark of cancer. Through increased understanding of the complex interactions between immunity and cancer, immunotherapy has emerged as a treatment modality for different types of cancer. Promising activity with immunotherapy has been reported in numerous malignancies, but challenges such as limited response rates and treatment resistance remain. Furthermore, outcomes with this therapeutic approach in hematologic malignancies are even more limited than in solid tumors. T-cell immunoglobulin domain and mucin domain 3 (TIM-3) has emerged as a potential immune checkpoint target in both solid tumors and hematologic malignancies. TIM-3 has been shown to promote immune tolerance, and overexpression of TIM-3 is associated with more aggressive or advanced disease and poor prognosis.

AREAS COVERED

This review examines what is currently known regarding the biology of TIM-3 and clinical implications of targeting TIM-3 in cancer. Particular focus is given to myeloid malignancies.

EXPERT OPINION

The targeting of TIM-3 is a promising therapeutic approach in cancers, including hematologic cancers such as myeloid malignancies which have not benefited much from current immunotherapeutic treatment approaches. We anticipate that with further clinical evaluation, TIM-3 blockade will emerge as an important treatment strategy in myeloid malignancies.

摘要

引言

免疫系统功能失调是癌症的一个标志。随着对免疫与癌症之间复杂相互作用的深入了解,免疫疗法已成为治疗不同类型癌症的一种治疗方式。在众多恶性肿瘤中都报道了免疫疗法具有有前景的活性,但仍存在诸如反应率有限和治疗耐药等挑战。此外,这种治疗方法在血液系统恶性肿瘤中的疗效比实体瘤更有限。T细胞免疫球蛋白结构域和粘蛋白结构域3(TIM-3)已成为实体瘤和血液系统恶性肿瘤中潜在的免疫检查点靶点。TIM-3已被证明可促进免疫耐受,TIM-3的过表达与更具侵袭性或晚期疾病以及不良预后相关。

涵盖领域

本综述探讨了目前关于TIM-3生物学的已知信息以及在癌症中靶向TIM-3的临床意义。特别关注髓系恶性肿瘤。

专家观点

靶向TIM-3是一种有前景的癌症治疗方法,包括髓系恶性肿瘤等血液系统癌症,这些癌症目前从免疫治疗方法中获益不多。我们预计,随着进一步的临床评估,TIM-3阻断将成为髓系恶性肿瘤的一种重要治疗策略。

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