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.