Fc Receptor-Like 1(FCRL1),a member of the FCRL family,contains two immunoreceptor tyrosinebased activation motifs(ITAMs)in its cytoplasmic domain and plays a critical role in B-cell biology.Its expression begins in pr...Fc Receptor-Like 1(FCRL1),a member of the FCRL family,contains two immunoreceptor tyrosinebased activation motifs(ITAMs)in its cytoplasmic domain and plays a critical role in B-cell biology.Its expression begins in pre-B-cells,dynamically shifts during B-cell development,and contributes to the regulation of human B-cell activation.Notably,FCRL1 is overexpressed in subsets of naive and memory B-cells,as well as in malignant B-cells,including those in diffuse large B-cell lymphoma(DLBCL),an aggressive and often treatment-resistant hematological malignancy.Among FCRL family members,FCRL1 stands out as a promising immunotherapeutic target due to its selective expression in malignant B-cells and its functional role in proliferation.Given the limited efficacy of current therapies for relapsed/refractory DLBCL,targeting FCRL1 could address an unmet clinical need by offering a novel,mechanism-based approach to modulate B-cell signaling and enhance anti-tumor immunity.This mini-review highlights the therapeutic potential of FCRL1-directed strategies,supporting their further exploration in preclinical models and future clinical trials for DLBCL and other B-cell malignancies.展开更多
基金supported by funding from the Veterans Administration(I01 BX006101-01)supported in part by funding from the Veterans Administration(IO1 BX001262)the recipient of RCS Award(IK6 BX005964)from the Department of Veterans Administration.
文摘Fc Receptor-Like 1(FCRL1),a member of the FCRL family,contains two immunoreceptor tyrosinebased activation motifs(ITAMs)in its cytoplasmic domain and plays a critical role in B-cell biology.Its expression begins in pre-B-cells,dynamically shifts during B-cell development,and contributes to the regulation of human B-cell activation.Notably,FCRL1 is overexpressed in subsets of naive and memory B-cells,as well as in malignant B-cells,including those in diffuse large B-cell lymphoma(DLBCL),an aggressive and often treatment-resistant hematological malignancy.Among FCRL family members,FCRL1 stands out as a promising immunotherapeutic target due to its selective expression in malignant B-cells and its functional role in proliferation.Given the limited efficacy of current therapies for relapsed/refractory DLBCL,targeting FCRL1 could address an unmet clinical need by offering a novel,mechanism-based approach to modulate B-cell signaling and enhance anti-tumor immunity.This mini-review highlights the therapeutic potential of FCRL1-directed strategies,supporting their further exploration in preclinical models and future clinical trials for DLBCL and other B-cell malignancies.
文摘目的:初步探讨慢性淋巴细胞白血病(chronic lymphocytic leukemia,CLL)患者外周血共抑制分子T细胞免疫球蛋白和ITIM结构域(T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain,TIGIT)和程序性细胞死亡受体1(programmed cell death protein 1,PD-1)在Tfh细胞上的表达变化特点及临床意义。方法:采用流式细胞术检测50例CLL患者、36例非CLL的慢性B淋巴细胞增殖疾病患者和30例健康者外周血Tfh细胞百分比和Tfh细胞上PD-1和TIGIT的水平,比较3组受试者的差异。分析CLL患者TIGIT+PD-1+Tfh细胞百分比与IPI评分分层的关系,以及与免疫球蛋白的相关性。结果:(1)与对照组比较,初诊CLL患者Tfh、PD-1+Tfh、TIGIT+Tfh、TIGIT+PD-1+Tfh、TIGIT+PD-1-Tfh和TIGIT-PD-1+Tfh细胞百分比明显增高,差异有统计学意义(P<0.05)。(2)TIGIT+PD-1+Tfh细胞在CLL-IPI预后分层低危组、中危组、高危组、极高危组比较分析结果,组间和组内两两比较差异均有统计学意义(P<0.05),随着预后分层增加TIGIT+PD-1+Tfh细胞水平逐渐增加。(3)受试者工作特征曲线结果显示,TIGIT+PD-1+Tfh细胞在CLL患者和非CLL患者的鉴别诊断中具有一定的诊断价值(P<0.05)。(4)Logistic回归分析显示,TIGIT+PD-1+Tfh细胞百分比是CLL发病的独立危险因素(P<0.05)。(5)CLL患者外周血中TIGIT+PD-1+Tfh与IgA、IgM、IgG均呈负相关(P<0.05)。结论:初诊CLL患者外周血TIGIT+PD-1+Tfh细胞百分比明显增加,Tfh细胞高表达共抑制分子TIGIT和PD-1参与CLL疾病的发生,并且与疾病的免疫球蛋白水平降低有关。
