利用内源性树突状细胞增强过继性 T 细胞疗法和检查点阻断的治疗效果。
Leveraging Endogenous Dendritic Cells to Enhance the Therapeutic Efficacy of Adoptive T-Cell Therapy and Checkpoint Blockade.
机构信息
National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital Herlev, Copenhagen, Denmark.
Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
出版信息
Front Immunol. 2020 Sep 25;11:578349. doi: 10.3389/fimmu.2020.578349. eCollection 2020.
Adoptive cell therapy (ACT), based on treatment with autologous tumor infiltrating lymphocyte (TIL)-derived or genetically modified chimeric antigen receptor (CAR) T cells, has become a potentially curative therapy for subgroups of patients with melanoma and hematological malignancies. To further improve response rates, and to broaden the applicability of ACT to more types of solid malignancies, it is necessary to explore and define strategies that can be used as adjuvant treatments to ACT. Stimulation of endogenous dendritic cells (DCs) alongside ACT can be used to promote epitope spreading and thereby decrease the risk of tumor escape due to target antigen downregulation, which is a common cause of disease relapse in initially responsive ACT treated patients. Addition of checkpoint blockade to ACT and DC stimulation might further enhance response rates by counteracting an eventual inactivation of infused and endogenously primed tumor-reactive T cells. This review will outline and discuss therapeutic strategies that can be utilized to engage endogenous DCs alongside ACT and checkpoint blockade, to strengthen the anti-tumor immune response.
过继细胞疗法(ACT)基于用自体肿瘤浸润淋巴细胞(TIL)衍生的或基因修饰的嵌合抗原受体(CAR)T 细胞进行治疗,已经成为治疗黑色素瘤和血液系统恶性肿瘤亚组患者的一种潜在的根治性疗法。为了进一步提高反应率,并扩大 ACT 在更多类型实体恶性肿瘤中的适用性,有必要探索和定义可以作为 ACT 辅助治疗的策略。ACT 时联合刺激内源性树突状细胞(DC)可用于促进表位扩展,从而降低因靶抗原下调而导致肿瘤逃逸的风险,这是最初对 ACT 治疗有反应的患者疾病复发的常见原因。在 ACT 和 DC 刺激中加入检查点阻断可能通过抵消输注和内源性启动的肿瘤反应性 T 细胞的最终失活,进一步提高反应率。本文将概述和讨论可用于 ACT 和检查点阻断时结合内源性 DC 的治疗策略,以增强抗肿瘤免疫反应。