CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tumor Microenvironment and Immunotherapy-Based Approaches in Mantle Cell Lymphoma.
Tumor Microenvironment and Immunotherapy-Based Approaches in Mantle Cell Lymphoma.
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套细胞淋巴瘤(MCL)是一种侵袭性B细胞非霍奇金淋巴瘤(NHL),其特征为t(11;14)(q13;q32)易位,且对利妥昔单抗-蒽环类化疗反应较差。以大剂量阿糖胞苷为基础的方案可带来持久缓解,但相当一部分MCL患者不适合强化治疗,适合接受新型靶向疗法(如BTK、蛋白酶体或BCL2抑制剂、免疫调节药物、双特异性抗体或CAR-T 细胞疗法)。多项研究从肿瘤生态系统角度开展探索,强调肿瘤微环境(TME)在MCL扩增和耐药中的关键作用,由此加深了对TME在MCL管理中的认识,并发现潜在靶点和生物标志物。事实上,靶向药物往往不仅作用于肿瘤B细胞,也会共同影响肿瘤微环境。本综述旨在简述MCL中TME生物学的现有认识,并介绍纳入TME因素的不同治疗策略研究结果。
Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) characterized by the translocation t(11;14) (q13;q32) and a poor response to rituximab-anthracycline-based chemotherapy. High-dose cytarabine-based regimens offer a durable response, but an important number of MCL patients are not eligible for intensive treatment and are ideal candidates for novel targeted therapies (such as BTK, proteasome or BCL2 inhibitors, Immunomodulatory Drugs (IMiDs), bispecific antibodies, or CAR-T cell therapy).
On the bench side, several studies aiming to integrate the tumor within its ecosystem highlighted a critical role of the tumor microenvironment (TME) in the expansion and resistance of MCL. This led to important insights into the role of the TME in the management of MCL, including potential targets and biomarkers.
Indeed, targeted agents often have a combined mechanism of action on the tumor B cell but also on the tumor microenvironment. The aim of this review is to briefly describe the current knowledge on the biology of the TME in MCL and expose the results of the different therapeutic strategies integrating the TME in this disease.
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