联合力量：用小分子抑制剂提高细胞免疫疗法的临床反应。

Joining Forces: Improving Clinical Response to Cellular Immunotherapies with Small-Molecule Inhibitors.

机构信息

QIMR Centre for Immunotherapy and Vaccine Development and Department of Immunology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.

QIMR Centre for Immunotherapy and Vaccine Development and Department of Immunology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; School of Medicine, University of Queensland, Brisbane, QLD, Australia.

出版信息

Trends Mol Med. 2021 Jan;27(1):75-90. doi: 10.1016/j.molmed.2020.09.005. Epub 2020 Sep 30.

DOI:10.1016/j.molmed.2020.09.005

PMID:33011081

Abstract

Adoptive T cell therapy (ACT) has emerged as a powerful therapeutic tool against both hematological and virus-associated cancers. However, extension of this success to solid cancers has been challenging owing to intratumoral mechanisms that induce a hostile immunosuppressive tumor microenvironment (TME). Delineating the impact of tumor-intrinsic adaptive resistance mechanisms on immune-based therapies is essential to improve long-term efficacy. We discuss the different tumor-intrinsic factors that lead to resistance to ACT. We highlight the potential of repurposing molecular targeted therapies to modulate immune responses and override intratumor resistance to ACT. Finally, we discuss the potential of combining targeted therapy and ACT as a new paradigm to improve the clinical efficacy of cancer therapeutics.

摘要

过继性 T 细胞疗法 (ACT) 已成为对抗血液系统和病毒相关癌症的有力治疗工具。然而，由于肿瘤内机制诱导了具有敌意的免疫抑制肿瘤微环境 (TME)，将这一成功扩展到实体瘤一直具有挑战性。阐明肿瘤内在适应性耐药机制对免疫治疗的影响对于提高长期疗效至关重要。我们讨论了导致 ACT 耐药的不同肿瘤内在因素。我们强调了重新利用分子靶向治疗来调节免疫反应并克服 ACT 肿瘤内耐药的潜力。最后，我们讨论了将靶向治疗与 ACT 相结合作为一种新范例以提高癌症治疗临床疗效的潜力。