FCGR3A 在位置 158 (V/F) 处呈现单核苷酸多态性，这影响其与抗体 (Abs) 的可结晶片段 (Fc) 的结合。 FcγRIIIa-158 V 同种异型具有最高的亲和力，并且与 IgG1 单克隆抗体 (mAb) 治疗的更好临床反应相关。我们比较了 B 细胞淋巴增殖性疾病患者队列中 FCGR3A-F158V 多态性的等位基因频率，包括多发性骨髓瘤 (MM)、意义未明的单克隆丙种球蛋白病 (MGUS)、非霍奇金淋巴瘤 (NHL) 和 B 细胞慢性淋巴瘤白血病（B-CLL）。 FCGR3A-158F 纯合子在 MM 和 MGUS 患者中富集并趋向于分别；但 B-CLL 和 NHL 患者都没有。我们发现 F/F 基因型 MM 患者骨髓中 CD8 T 细胞和静息记忆 CD4 T 细胞的浓度显着降低，与巨噬细胞百分比的增加相关。相反，V/V 纯合子患者的自然杀伤细胞有所增加。这表明 FCGR3A-F/F 纯合子患者的免疫微环境失调。然而，我们没有观察到联合或不联合化疗联合达雷妥尤单抗（一种直接针对 CD38 的 IgG1 单克隆抗体）后的反应差异。我们的研究结果表明 FCGR3A F158V 多态性可以调节免疫环境并影响肿瘤浆细胞的发育。© 2024 作者。经泰勒许可出版

FCGR3A presents a single nucleotide polymorphism at location 158 (V/F), which affects its binding to the fragment crystallizable (Fc) of antibodies (Abs). FcγRIIIa-158 V allotype has the highest affinity and is associated with a better clinical response to IgG1 monoclonal Abs (mAb) treatment. We compared the allele frequency of FCGR3A-F158V polymorphism in cohorts of patients with B-cell lymphoproliferative disorders, including multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), non-Hodgkin lymphoma (NHL), and B-cell chronic leukemia (B-CLL). FCGR3A-158F homozygous were enriched and tended to be in MM and MGUS patients, respectively; but neither in B-CLL nor in NHL patients. We identified a significantly lower concentration of CD8 T-cells and resting memory CD4 T-cells in MM patients bone marrow with the F/F genotype, associated with an increase in the macrophage percentage. In contrast, natural killer cells increased in V/V homozygous patients. This suggests a deregulation of the immune microenvironment in FCGR3A-F/F homozygous patients. However, we did not observe difference in response following treatment combining chemotherapy associated or not with daratumumab, an IgG1 mAb direct against CD38. Our findings suggest that FCGR3A F158V polymorphism can regulate the immune environment and affect the development of tumor plasma cells.© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.