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:Immune checkpoint blockade and CAR T-cell therapy in T-cell/histiocyte-rich large B-cell lymphoma: Challenges and opportunities.
Immune checkpoint blockade and CAR T-cell therapy in T-cell/histiocyte-rich large B-cell lymphoma: Challenges and opportunities.
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富含T细胞/组织细胞的大B细胞淋巴瘤(THRLBCL)是一种高度侵袭性大B细胞淋巴瘤,其特征为恶性B细胞稀少,而反应性T细胞和组织细胞密集浸润。THRLBCL独特的肿瘤微环境(TME)具有广泛免疫浸润及PD-L1高表达,给免疫治疗带来显著挑战。本综述探讨免疫检查点抑制剂(ICI)和嵌合抗原受体(CAR)T细胞疗法治疗THRLBCL的潜力及耐药机制。由于TME具有免疫抑制特征,ICI显示出治疗希望;CAR-T 疗法的疗效则有限,常受原发耐药和早期复发影响。CAR-T 联合ICI及布鲁顿酪氨酸激酶(BTK)抑制剂,以及开发靶向多种抗原的新型CAR构建体,可能改善治疗结局。仍需进一步前瞻性研究证实这些策略,并改善这一难治淋巴瘤亚型的预后。
T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a highly aggressive large B-cell lymphoma defined by a paucity of malignant B cells amidst a dense infiltrate of reactive T cells and histiocytes. The unique tumor microenvironment (TME) of THRLBCL, marked by extensive immune infiltration and high PD-L1 expression, poses significant challenges for immunotherapies. This review explores the therapeutic potential and resistance mechanisms of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T-cell therapy in THRLBCL.
While ICIs show promise due to the immune-suppressive nature of the TME, CAR T-cell therapy has demonstrated limited efficacy, often hindered by primary resistance and early relapse. Combining CAR T-cell therapy with ICIs and Bruton tyrosine kinase (BTK) inhibitors and developing novel CAR constructs targeting multiple antigens are potential strategies to enhance treatment outcomes.
Further prospective studies are essential to corroborate these strategies and improve the prognosis for this challenging lymphoma subtype.
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