让冷肿瘤变热的免疫肿瘤微环境调节剂

IF 20.1 1区 医学 Q1 ONCOLOGY
Gholam-Reza Khosravi, Samaneh Mostafavi, Sanaz Bastan, Narges Ebrahimi, Roya Safari Gharibvand, Nahid Eskandari
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引用次数: 0

摘要

根据肿瘤微环境(TME)中细胞毒性免疫细胞的存在和排列,可以将肿瘤分为不同的免疫分型。热肿瘤的特点是免疫活性增强,对免疫检查点抑制剂(ICIs)反应灵敏,与冷肿瘤形成鲜明对比,后者缺乏免疫浸润,对治疗仍有抵抗力。为了克服肿瘤细胞采用的免疫逃避机制,新型免疫调节剂应运而生,特别是针对细胞毒性T淋巴细胞相关蛋白4(CTLA-4)和程序性细胞死亡蛋白1/程序性死亡配体1(PD-1/PD-L1)的ICIs。这些药物能破坏抑制信号,重新激活免疫系统,将冷肿瘤转化为热肿瘤,促进有效的抗肿瘤反应。然而,挑战依然存在,包括免疫疗法的原发性耐药性、自身免疫副作用和肿瘤反应异质性。要应对这些挑战,需要创新的策略、更深入的机理研究以及综合的免疫干预措施,以提高免疫疗法的有效性。在癌症医学领域,免疫冷冻肿瘤是一个巨大的障碍,因此了解TME并利用其重新编程免疫反应的潜力至关重要。这篇综述揭示了在寻求更有效、更安全的癌症治疗策略方面的当前进展和未来方向,为免疫抗性肿瘤患者带来了希望。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Immunologic tumor microenvironment modulators for turning cold tumors hot

Immunologic tumor microenvironment modulators for turning cold tumors hot

Tumors can be classified into distinct immunophenotypes based on the presence and arrangement of cytotoxic immune cells within the tumor microenvironment (TME). Hot tumors, characterized by heightened immune activity and responsiveness to immune checkpoint inhibitors (ICIs), stand in stark contrast to cold tumors, which lack immune infiltration and remain resistant to therapy. To overcome immune evasion mechanisms employed by tumor cells, novel immunologic modulators have emerged, particularly ICIs targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1/programmed death-ligand 1(PD-1/PD-L1). These agents disrupt inhibitory signals and reactivate the immune system, transforming cold tumors into hot ones and promoting effective antitumor responses. However, challenges persist, including primary resistance to immunotherapy, autoimmune side effects, and tumor response heterogeneity. Addressing these challenges requires innovative strategies, deeper mechanistic insights, and a combination of immune interventions to enhance the effectiveness of immunotherapies. In the landscape of cancer medicine, where immune cold tumors represent a formidable hurdle, understanding the TME and harnessing its potential to reprogram the immune response is paramount. This review sheds light on current advancements and future directions in the quest for more effective and safer cancer treatment strategies, offering hope for patients with immune-resistant tumors.

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来源期刊
Cancer Communications
Cancer Communications Biochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
25.50
自引率
4.30%
发文量
153
审稿时长
4 weeks
期刊介绍: Cancer Communications is an open access, peer-reviewed online journal that encompasses basic, clinical, and translational cancer research. The journal welcomes submissions concerning clinical trials, epidemiology, molecular and cellular biology, and genetics.
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