Division of Paediatric Oncology and Paediatric Surgery, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Front Immunol. 2021 Mar 4;12:582539. doi: 10.3389/fimmu.2021.582539. eCollection 2021.
The immune system plays a major role in recognizing and eliminating malignant cells, and this has been exploited in the development of immunotherapies aimed at either activating or reactivating the anti-tumor activity of a patient's immune system. A wide range of therapeutic approaches involving T lymphocytes, such as programmed cell death protein ligand-1 (PDL-1) inhibitors, cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) blockers, and CD19-targeted T-cell therapy through chimeric antigen receptor (CAR)-T cells or CD19/CD3 bi-specific T-cell engagers, have been introduced to the field of oncology, leading to significant improvements in overall survival of adult cancer patients. During the past few years, the availability and approval of T-cell based immunotherapies have become a reality also for the treatment of childhood cancers. However, the distribution, ratio of regulatory to effector cells and the quality of T-cell responses early in life are distinct from those during adolescence and adulthood, raising the possibility that these differences impact the efficacy of immunotherapy. Herein we provide a brief overview of the properties of conventional T cell subsets during early life. Focusing on the most common cancer type during childhood, acute lymphoblastic leukemia (ALL), we describe how current conventional therapies used against ALL influence the T-cell compartment of small children. We describe early life T-cell responses in relation to immunotherapies engaging T-cell anticancer reactivity and present our opinion that it is not only immaturity of the adaptive immune system, but also the impact of an immunosuppressive environment that may prove disadvantageous in the setting of immunotherapies targeting pediatric cancer cells.
免疫系统在识别和消除恶性细胞方面发挥着重要作用，这在开发旨在激活或重新激活患者免疫系统抗肿瘤活性的免疫疗法方面得到了利用。涉及 T 淋巴细胞的广泛治疗方法，如程序性细胞死亡蛋白配体-1（PDL-1）抑制剂、细胞毒性 T 淋巴细胞相关蛋白-4（CTLA-4）阻滞剂，以及通过嵌合抗原受体（CAR）-T 细胞或 CD19/CD3 双特异性 T 细胞衔接器进行的 CD19 靶向 T 细胞疗法，已被引入肿瘤学领域，导致成年癌症患者的总生存率显著提高。在过去的几年中，T 细胞为基础的免疫疗法的可用性和批准也已成为治疗儿童癌症的现实。然而，T 细胞在生命早期的分布、调节性与效应细胞的比例和 T 细胞反应的质量与青春期和成年期不同，这使得这些差异可能影响免疫疗法的疗效成为可能。在此，我们简要概述了生命早期常规 T 细胞亚群的特性。本文聚焦于儿童期最常见的癌症类型——急性淋巴细胞白血病（ALL），描述了目前针对 ALL 所使用的常规疗法如何影响幼儿的 T 细胞群。我们描述了与针对癌症的 T 细胞反应的免疫疗法相关的生命早期 T 细胞反应，并提出了这样的观点：在针对儿科癌细胞的免疫疗法中，不利因素不仅是适应性免疫系统的不成熟，还有免疫抑制环境的影响。
