Work

Synergistic antitumor effects of combined pembrolizumab and anlotinib via EGFR inhibition and tumor microenvironment remodeling in high-grade serous ovarian cancer

Year: 2026

Type: article

Abstract: Background High-grade serous ovarian cancer (HGSOC) remains difficult to treat, particularly in platinum-resistant or recurrent cases. Despite ongoing clinical trials investigating pembrolizumab combined with anlotinib, the synergistic mechanisms of this regimen are poorly understood. Methods This study constructed humanized patient-derived xenograft models via implanting HGSOC tumor cells into NSG mice and subsequently infusing human peripheral blood mononuclear cells to dissect synergistic mechanisms. Results Relative to controls and pembrolizumab monotherapy, combination therapy raised the fractions of CD4 + T cells and CD8 + /NK cells while decreasing myeloid-derived suppressor cell abundance. Enhanced cell-cell interactions from monocyte and CD8 + /NK-cell senders to epithelial targets were observed in the combination group. Upregulation of GRN-SORT1 signaling mediated communication between myeloid subclusters 1, 7 and epithelial subclusters 0, 2, 3, whereas CCL7-CCR1 signaling was activated between myeloid subcluster 7 and lymphocyte subcluster 0. A decreased Treg proportion was also achieved under combined treatment. Multicolor immunofluorescence of patient HGSOC tissues showed close spatial contacts between CD14 + CCL7 + monocytes and CD8 + CCR1 + T cells, and CCL7 as well as CCR1 expression positively correlated with intratumoral CD8 + T-cell infiltration. Conclusion These findings suggest that pembrolizumab and anlotinib may synergize through both limiting tumor-promoting pathways and enhancing anti-tumor immunity. This combinatorial regimen may represent a promising therapeutic strategy for improving clinical outcomes in HGSOC patients.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2026.1880902