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:T-cell/histiocyte-rich large B-cell lymphoma, insights into prognosis and treatment complexity in the context of immunotherapeutics.
T-cell/histiocyte-rich large B-cell lymphoma, insights into prognosis and treatment complexity in the context of immunotherapeutics.
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富含T细胞/组织细胞的大B细胞淋巴瘤(THRLBCL)是弥漫大B细胞淋巴瘤(DLBCL)中罕见且生物学特征独特的亚型,其特征是在显著炎症性微环境中仅有少量肿瘤性B细胞。该病既往被认为预后不良,但当代报告显示,其结局可与DLBCL非特指型(DLBCL-NOS)相当甚至更好,尤其是在采用化学免疫治疗时。与匹配的DLBCL队列相比,自体造血细胞移植(auto-HCT)使复发患者获得较好的无进展生存期和总生存期。靶向CD19的CAR-T 细胞疗法在THRLBCL中的疗效有限,复发率高且缓解不持久,可能与PD-1/PD-L1通路激活所致的免疫抑制性肿瘤微环境有关。若干病例系列和转化研究支持对部分患者使用免疫检查点阻断,但仍需前瞻性验证。双特异性抗体、tafasitamab-来那度胺及抗体药物偶联物在R/R DLBCL中显示前景,但THRLBCL患者在这些关键试验中代表不足。本综述总结THRLBCL预后的现有认识,并强调需要深入理解其生物学特征和免疫逃逸机制,以开发新的、基于生物学特征的策略,改善复发阶段患者结局。
T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare and biologically distinct subtype of diffuse large B-cell lymphoma (DLBCL). It is marked by rare neoplastic B-cells within a prominent inflammatory microenvironment. Historically it was associated with poor prognosis but contemporary reports show outcomes comparable if not better than DLBCL-NOS, especially with the use of chemo-immunotherapies. Autologous stem cell transplantation (auto-HCT) demonstrated favorable progression-free and overall survival in relapsed patients in comparison to matched DLBCL cohorts. The efficacy of CD19-directed CAR T-cell therapy in THRLBCL has been limited, with high relapse rates and poor durability of response, likely due to an immunosuppressive tumor microenvironment characterized by PD-1/PD-L1 pathway activation.
Several case series and translational studies support the use of immune checkpoint blockade in selected patients, although prospective validation is needed. While bispecific antibodies, tafasitamab-lenalidomide, and antibody-drug conjugates show promise in R/R DLBCL, THRLBCL patients remain underrepresented in these pivotal trials.
This review summarizes current insights into the prognosis of THRLBCL and underscores the need for novel, biologically informed strategies to improve outcomes in the relapsed setting through a deeper understanding of its biology and immune evasion mechanisms.
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