Guillaume J, Perzolli A, Boes M
Centre for Translational Immunology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
Princess Mȧxima Centre for Paediatric Oncology, Utrecht, The Netherlands.
Immunother Adv. 2023 Dec 11;4(1):ltad028. doi: 10.1093/immadv/ltad028. eCollection 2024.
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.
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。仍有几个挑战需要解决，其中包括相当一部分癌症患者的治疗反应不完全治愈、肿瘤产生治疗抗性以及出现诸如炎症和自身免疫并发症等不良反应。与成人肿瘤相比，儿科肿瘤通常对免疫疗法的反应较低。尽管其根本原因尚未完全了解，但肿瘤避免免疫识别的一种已知机制是通过降低主要组织相容性复合体I类（MHC-I）复合物的细胞表面表达。因此，MHC-I对新抗原的呈递减少阻碍了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。MHC-I下调确实常常与较差的预后和对免疫疗法的反应减弱相关。了解不同类型儿科和成人肿瘤中MHC-I下调的潜在机制对于制定恢复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。
