Synergistic antitumor effects of combined pembrolizumab and anlotinib via EGFR inhibition and tumor microenvironment remodeling in high-grade serous ovarian cancer
8 affiliations
- 1Department of Radiation Oncology, The Affiliated Hospital of Qingdao University
- 2Department of Pathology, The Affiliated Hospital of Qingdao University
- 3School of Pharmacy, Qingdao University
- 4School of Information and Software Engineering, University of Electronic Science and Technology of China
- 5School of Computer Science and Software Engineering, Southwest Petroleum University
- 6The First People’s Hospital of Kashi
- 7Department of Oncology, the First People’s Hospital of Kashgar Prefecture
- 8Department of Pharmacy, The Affiliated Hospital of Qingdao University
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.
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BibTeX
@article{yin2026synergistic,
title = {{Synergistic antitumor effects of combined pembrolizumab and anlotinib via EGFR inhibition and tumor microenvironment remodeling in high-grade serous ovarian cancer}},
author = {Xiaoyang Yin and Longxiao Zhang and Yidan Mu and Guangping Li and Xiaoyu Li and Desheng Zheng and Xuwei Tian and Reziya Emir and Yu Liang and Peng Zhao and Man Jiang},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1880902},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1880902/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Synergistic antitumor effects of combined pembrolizumab and anlotinib via EGFR inhibition and tumor microenvironment remodeling in high-grade serous ovarian cancer
AU - Xiaoyang Yin
AU - Longxiao Zhang
AU - Yidan Mu
AU - Guangping Li
AU - Xiaoyu Li
AU - Desheng Zheng
AU - Xuwei Tian
AU - Reziya Emir
AU - Yu Liang
AU - Peng Zhao
AU - Man Jiang
PY - 2026
DA - 2026/10/19
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1880902
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1880902/full
AB - 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.
SN - 2234-943X
ER -