Emerging Roles of Fc Receptor-Like 1 in Immunotherapy of Diffuse Large B-Cell Lymphoma

Fc Receptor-Like 1 (FCRL1), a member of the FCRL family, contains two immunoreceptor tyrosine-based 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.