Strategies to overcome low MHC-I expression in paediatric and adult tumours.

IF 4.1 Q2 IMMUNOLOGY Immunotherapy advances Pub Date : 2023-12-11 eCollection Date: 2024-01-01 DOI:10.1093/immadv/ltad028
J Guillaume, A Perzolli, M Boes
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Abstract

Immunotherapy has made significant advancements in cancer treatments, improving patients' survival rates and quality of life. Several challenges still need to be addressed, which include the considerable fraction of incomplete curative responses in cancer patients, the development of therapy resistance by tumours, and the occurrence of adverse effects, such as inflammatory and autoimmune complications. Paediatric tumours usually exhibit lower responsiveness to immunotherapies compared to adult tumours. Although the underlying reasons are not yet fully understood, one known mechanism by which tumours avoid immune recognition is through reduced cell surface expression of major histocompatibility complex class I (MHC-I) complexes. Accordingly, the reduced presentation of neoantigens by MHC-I hinders the recognition and targeting of tumour cells by CD8+ T cells, impeding T-cell-mediated cytotoxic anti-tumour responses. MHC-I downregulation indeed often correlates with a poorer prognosis and diminished response to immunotherapy. Understanding the mechanisms underlying MHC-I downregulation in different types of paediatric and adult tumours is crucial for developing strategies to restore MHC-I expression and enhance anti-tumour immune responses. We here discuss progress in MHC-I-based immunotherapies against cancers.

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克服儿童和成人肿瘤中 MHC-I 低表达的策略。
免疫疗法在癌症治疗方面取得了重大进展,提高了患者的生存率和生活质量。但仍有一些挑战需要解决,其中包括癌症患者中存在相当大比例的不完全治愈反应、肿瘤产生抗药性以及出现炎症和自身免疫并发症等不良反应。与成人肿瘤相比,儿童肿瘤对免疫疗法的反应性通常较低。虽然其根本原因尚不完全清楚,但肿瘤避免免疫识别的一个已知机制是细胞表面主要组织相容性复合物 I 类(MHC-I)复合物的表达减少。因此,MHC-I 对新抗原的呈现减少,阻碍了 CD8+ T 细胞对肿瘤细胞的识别和靶向,从而阻碍了 T 细胞介导的细胞毒性抗肿瘤反应。事实上,MHC-I的下调往往与预后较差和对免疫疗法的反应减弱相关。了解不同类型儿童和成人肿瘤中 MHC-I 下调的机制对于制定恢复 MHC-I 表达和增强抗肿瘤免疫反应的策略至关重要。我们在此讨论基于 MHC-I 的癌症免疫疗法的进展。
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审稿时长
7 weeks
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