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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immune microenvironment and its influence on CAR-T treatment outcomes in B-NHL.
Immune microenvironment and its influence on CAR-T treatment outcomes in B-NHL.
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B 细胞非霍奇金淋巴瘤(B-NHL)具有高度异质性。目前 CAR-T 细胞已广泛用于 B 细胞淋巴瘤治疗,完全缓解率可达 40%–60%。越来越多研究显示,免疫微环境在 B-NHL 发生和发展中发挥重要作用,但肿瘤微环境如何影响 CAR-T 治疗 B-NHL 的效果仍不清楚。研究者分析本中心 36 名复发/难治性弥漫性大 B 细胞淋巴瘤(R/R DLBCL)患者的 44 份肿瘤组织活检样本,探索与 CAR-T 疗效改善相关的微环境免疫细胞组成。中位随访时间为 8.5 个月。研究分析不同细胞对患者生存的影响,识别出多个预后保护因素和风险因素。其中 Treg 细胞是与 CAR-T 疗效相关的关键预后保护因素(P<0.009;HR=0.32)。
进一步比较同一患者 CAR-T 治疗前后的肿瘤活检发现,Treg 细胞较多与 CAR-T 疗效较好和 CAR-T 持续性相关。CAR-T 治疗后未检出残留 CAR-T 细胞的活检样本中 Treg 细胞更多。无残留 CAR-T 细胞组总缓解率为 61.5%(n=8),包括完全缓解 30.8%(n=4)、部分缓解 30.8%(n=4)、疾病稳定 7.7%(n=1)和疾病进展 30.8%(n=4);残留 CAR-T 细胞组则有 1 名部分缓解患者(25%)。
B-cell non-Hodgkin's lymphoma (B-NHL) is a highly heterogeneous tumor. Currently, CAR-T cells have been widely used in the treatment of B-cell lymphomas, with a complete response rate reaching 40%-60%. More and more studies have shown that the immune microenvironment plays an important role in the occurrence and development of B-NHL.
However, it is still unclear what role the tumor microenvironment plays in the effect of CAR-T therapy on B-NHL.
We analyzed the components of 44 tumor tissue biopsy samples from 36 patients with relapsed or refractory Diffuse large B-cell lymphoma (R/R DLBCL) in our center to explore the immune cell components in the tumor microenvironment that correlated with improved clinical outcomes of CAR-T therapy. The median follow-up time was 8. 5 months.
We analyzed the impact of various cells on patient survival and identified multiple prognostic protective factors and risk factors. Among them, Treg cells (P < 0. 009; HR = 0. 32) are a key prognostic protective factor that associated with the efficacy of CAR-T therapy.
Further analysis of tumor biopsy samples before and after CAR-T treatment in the same patients revealed that higher Treg cells were associated with the better CAR-T efficacy and were associated with sustained CAR-T persistence. There were more Treg cells in biopsy samples without CAR-T cells remaining after CAR-T treatment.
The overall response rate in non-residual CAR-T cells group was 61. 5% (n = 8), consisting of CR (30. 8%, n = 4), PR (30. 8%, n = 4), SD (7. 7%, n = 1), and PD (30. 8%, n = 4) compared to the residual CAR-T cells group (PR: n = 1, 25%).
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