Tumor-associated macrophages: untapped molecular targets to improve T cell-based immunotherapy

IF 33.9 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Rui M. L. Coelho, Reno Debets, Dora Hammerl
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引用次数: 0

Abstract

T cell responses are generally curtailed by suppressive mechanisms within the tumor microenvironment (TME) that prevent T cell infiltration and function. Consequently, T cell-based therapies for solid tumors have yielded limited and often non-durable clinical responses. Tumors develop a hostile TME, where tumor-associated macrophages (TAMs) that initially support T cells are converted into immune suppressive TAMs that facilitate tumor evasion from T cell control. In fact, immune suppressive TAMs represent a dominant fraction of immune cells within the TME and their presence is associated with poor prognosis and resistance to immunotherapy. Often in close contact with effector T cells, TAMs directly suppress CD8+ T cells through mechanisms involving metabolic mediators, co-signaling receptors, their ligands and/or cytokines. Here, we revisit molecular interactions behind TAM-mediated suppression of T cell responses and address the potential targeting of such molecules and pathways to re-boost anti-tumor T cell immunity. This perspective, focusing on molecular interactions between TAM and T cells, may aid the improvement of T cell-based therapies for solid tumors.
肿瘤相关巨噬细胞:改善T细胞免疫治疗的未开发分子靶点
T细胞反应通常被肿瘤微环境(TME)内阻止T细胞浸润和功能的抑制机制所抑制。因此,以T细胞为基础的实体瘤治疗产生了有限的临床反应,而且往往不是持久的。肿瘤发展为敌对的TME,其中最初支持T细胞的肿瘤相关巨噬细胞(tam)转化为免疫抑制性tam,促进肿瘤逃避T细胞的控制。事实上,免疫抑制性tam代表了TME中免疫细胞的主要部分,它们的存在与预后不良和免疫治疗抵抗有关。tam通常与效应T细胞密切接触,通过代谢介质、共信号受体及其配体和/或细胞因子等机制直接抑制CD8+ T细胞。在这里,我们回顾了tam介导的T细胞反应抑制背后的分子相互作用,并解决了这些分子和途径的潜在靶向性,以重新增强抗肿瘤T细胞免疫。这一观点关注TAM与T细胞之间的分子相互作用,可能有助于改进基于T细胞的实体瘤治疗方法。
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来源期刊
Molecular Cancer
Molecular Cancer 医学-生化与分子生物学
CiteScore
54.90
自引率
2.70%
发文量
224
审稿时长
2 months
期刊介绍: Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer. The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies. Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.
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