双阴性T细胞在血液系统恶性肿瘤中的应用:最新进展与未来方向
Application of double-negative T cells in haematological malignancies: recent progress and future directions.
作者信息
Chen Xingchi, Wang Dongyao, Zhu Xiaoyu
机构信息
Department of hematology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.
Blood and Cell Therapy Institute, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.
出版信息
Biomark Res. 2022 Mar 14;10(1):11. doi: 10.1186/s40364-022-00360-w.
Haematologic malignancies account for a large proportion of cancers worldwide. The high occurrence and mortality of haematologic malignancies create a heavy social burden. Allogeneic haematopoietic stem cell transplantation is widely used in the treatment of haematologic malignancies. However, graft-versus-host disease and relapse after allogeneic haematopoietic stem cell transplantation are inevitable. An emerging treatment method, adoptive cellular therapy, has been effectively used in the treatment of haematologic malignancies. T cells, natural killer (NK) cells and tumour-infiltrating lymphocytes (TILs) all have great potential in therapeutic applications, and chimeric antigen receptor T (CAR-T) cell therapy especially has potential, but cytokine release syndrome and off-target effects are common. Efficient anticancer measures are urgently needed. In recent years, double-negative T cells (CD3CD4CD8) have been found to have great potential in preventing allograft/xenograft rejection and inhibiting graft-versus-host disease. They also have substantial ability to kill various cell lines derived from haematologic malignancies in an MHC-unrestricted manner. In addition, healthy donor expanded double-negative T cells retain their antitumour abilities and ability to inhibit graft-versus-host disease after cryopreservation under good manufacturing practice (GMP) conditions, indicating that double-negative T cells may be able to be used as an off-the-shelf product. In this review, we shed light on the potential therapeutic ability of double-negative T cells in treating haematologic malignancies. We hope to exploit these cells as a novel therapy for haematologic malignancies.
血液系统恶性肿瘤在全球癌症中占很大比例。血液系统恶性肿瘤的高发病率和死亡率造成了沉重的社会负担。异基因造血干细胞移植广泛应用于血液系统恶性肿瘤的治疗。然而,异基因造血干细胞移植后的移植物抗宿主病和复发是不可避免的。一种新兴的治疗方法——过继性细胞疗法,已有效地用于血液系统恶性肿瘤的治疗。T细胞、自然杀伤(NK)细胞和肿瘤浸润淋巴细胞(TIL)在治疗应用中都具有很大潜力,尤其是嵌合抗原受体T(CAR-T)细胞疗法,但细胞因子释放综合征和脱靶效应很常见。迫切需要高效的抗癌措施。近年来,已发现双阴性T细胞(CD3CD4CD8)在预防同种异体移植/异种移植排斥反应和抑制移植物抗宿主病方面具有很大潜力。它们还具有以MHC非限制性方式杀伤各种血液系统恶性肿瘤来源细胞系的强大能力。此外,健康供体扩增的双阴性T细胞在良好生产规范(GMP)条件下冷冻保存后仍保留其抗肿瘤能力和抑制移植物抗宿主病的能力,这表明双阴性T细胞可能能够用作现成产品。在本综述中,我们阐述了双阴性T细胞在治疗血液系统恶性肿瘤方面的潜在治疗能力。我们希望开发这些细胞作为血液系统恶性肿瘤的一种新型疗法。