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The following is a summary of “FcγR3A polymorphism influences natural killer cell activation and response to anti-PD-L1 (avelumab) in gestational trophoblastic neoplasia,” published in the April 2025 issue of American Journal of Obstetrics & Gynecology by Msika et al. 

Avelumab, an anti-PD-L1 monoclonal antibody, showed a 53% cure rate with good tolerance in low-risk gestational trophoblastic neoplasia, offering a potential alternative to conventional chemotherapy.  

Researchers conducted a retrospective study to examine the role of antibody-dependent cell-mediated cytotoxicity in avelumab efficacy for gestational trophoblastic neoplasia and to assess whether FcγR3A affinity polymorphism predicted treatment response.  

They analyzed PD-L1 expression in tumors and natural killer cell phenotypes in gestational trophoblastic neoplasia using transcriptomic and proteomic methods. The JEG-3 choriocarcinoma cells were cocultured with human natural killer cells with and without avelumab. FcγR3A functional polymorphism effects on natural killer cell activation and JEG-3 cell viability were evaluated. Data from the TROPHIMMUN trial were re-analyzed to assess the impact of FcγR3A polymorphism on response to avelumab (TROPHIMMUN trial).  

The results showed that FcγR3A-positive natural killer cells infiltrated PD-L1-expressing gestational trophoblastic neoplasia. In vitro, avelumab-coated JEG-3 choriocarcinoma cells triggered natural killer cell activation, leading to JEG-3 cell destruction. Removing the Fc portion of avelumab abolished natural killer cell activation, confirming the role of Fcγ receptors. High-affinity FcγR3A polymorphism was linked to improving in vitro response to avelumab. Consistently, individuals homozygous for the high-affinity FcγR3A polymorphism in the TROPHIMMUN trial showed better clinical response to avelumab.  

Investigators concluded that antibody-dependent cell-mediated cytotoxicity contributed to avelumab’s therapeutic effect in gestational trophoblastic neoplasia, patient response was influenced by the FcγR3A polymorphism, which could serve as a biomarker to identify patients resistant to monochemotherapy that would most likely respond to avelumab. 

Source: ajog.org/article/S0002-9378(24)01046-9/fulltext