A New Strategy for the Treatment of Advanced Ovarian Cancer: Utilizing Nanotechnology to Regulate the Tumor Microenvironment

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2025 Feb 27

PMID 40013141

Authors

Zixuan Xiong

Yichun Huang

Shulong Cao

Xuqun Huang

Haiyuan Zhang

Affiliations

Soon will be listed here.

Abstract

Advanced ovarian cancer (AOC) is prone to recurrence, which can be attributed to drug resistance. Drug resistance may be related to the tumor microenvironment (TME), including the immune and non-immune TME. In the immune TME, the immune effector cells such as dendritic cells (DCs), M1-like tumor-associated macrophages (M1-TAMs), and T cells are inhibited. In contrast, immunosuppressive cells such as M2-like tumor-associated macrophages (M2-TAMs), myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs) are activated. These changes make it difficult to produce immune effects and affect the efficacy of chemo-immunotherapy. In the non-immune TME, mechanisms such as apoptosis inhibition, DNA damage response (DDR), and epithelial-mesenchymal transition (EMT) can promote tumor growth, metastasis, and drug resistance. Despite the challenges posed by the TME in the treatment of AOC, the unique biological advantages of nanoparticles (NPs) make it possible to regulate the TME. NPs can stimulate the immune responses of M1-TAMs, DCs, and T cells while reducing the infiltration of immune suppressive cells such as M2-TAMs and Tregs, thereby regulating the AOC immune TME. In addition, NPs can regulate the non-immune TME by reducing apoptosis in AOC cells, inhibiting homologous recombination (HR) repair, reversing EMT, and achieving the effect of reversing drug resistance. In summary, the application of NPs provides some new venues for clinical treatment in AOC.

References

Raghavan S, Mehta P, Xie Y, Lei Y, Mehta G . Ovarian cancer stem cells and macrophages reciprocally interact through the WNT pathway to promote pro-tumoral and malignant phenotypes in 3D engineered microenvironments. J Immunother Cancer. 2019; 7(1):190. PMC: 6642605. DOI: 10.1186/s40425-019-0666-1. View

Ocansey D, Qian F, Cai P, Ocansey S, Amoah S, Qian Y . Current evidence and therapeutic implication of PANoptosis in cancer. Theranostics. 2024; 14(2):640-661. PMC: 10758053. DOI: 10.7150/thno.91814. View

Lv X, Song J, Xue K, Li Z, Li M, Zahid D . Core fucosylation of copper transporter 1 plays a crucial role in cisplatin-resistance of epithelial ovarian cancer by regulating drug uptake. Mol Carcinog. 2019; 58(5):794-807. DOI: 10.1002/mc.22971. View

Vasan N, Baselga J, Hyman D . A view on drug resistance in cancer. Nature. 2019; 575(7782):299-309. PMC: 8008476. DOI: 10.1038/s41586-019-1730-1. View

Suurs F, Lorenczewski G, Bailis J, Stienen S, Friedrich M, Lee F . Mesothelin/CD3 half-life extended bispecific T-cell engager molecule shows specific tumor uptake and distributes to mesothelin and CD3 expressing tissues. J Nucl Med. 2021; . PMC: 8612194. DOI: 10.2967/jnumed.120.259036. View

Peng S, Xiao F, Chen M, Gao H . Tumor-Microenvironment-Responsive Nanomedicine for Enhanced Cancer Immunotherapy. Adv Sci (Weinh). 2021; 9(1):e2103836. PMC: 8728817. DOI: 10.1002/advs.202103836. View

Chen Y, Li F, Li D, Liu W, Zhang L . Atezolizumab and blockade of LncRNA PVT1 attenuate cisplatin resistant ovarian cancer cells progression synergistically via JAK2/STAT3/PD-L1 pathway. Clin Immunol. 2021; 227:108728. DOI: 10.1016/j.clim.2021.108728. View

Qiu M, Chen J, Huang X, Li B, Zhang S, Liu P . Engineering Chemotherapeutic-Augmented Calcium Phosphate Nanoparticles for Treatment of Intraperitoneal Disseminated Ovarian Cancer. ACS Appl Mater Interfaces. 2022; 14(19):21954-21965. DOI: 10.1021/acsami.2c02552. View

Zheng J, Sun Y, Long T, Yuan D, Yue S, Zhang N . Sonosensitizer nanoplatform-mediated sonodynamic therapy induced immunogenic cell death and tumor immune microenvironment variation. Drug Deliv. 2022; 29(1):1164-1175. PMC: 9004507. DOI: 10.1080/10717544.2022.2058653. View

10.

Gong J, Xing C, Wang L, Xie S, Xiong W . L-Tetrahydropalmatine enhances the sensitivity of human ovarian cancer cells to cisplatin via microRNA-93/PTEN/Akt cascade. J BUON. 2019; 24(2):701-708. View

11.

Li X, Wang S, Mu W, Barry J, Han A, Carpenter R . Reactive oxygen species reprogram macrophages to suppress antitumor immune response through the exosomal miR-155-5p/PD-L1 pathway. J Exp Clin Cancer Res. 2022; 41(1):41. PMC: 8793215. DOI: 10.1186/s13046-022-02244-1. View

12.

Derynck R, Zhang Y . Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 2003; 425(6958):577-84. DOI: 10.1038/nature02006. View

13.

Chen W, Dai X, Chen Y, Tian F, Zhang Y, Zhang Q . Significance of STAT3 in Immune Infiltration and Drug Response in Cancer. Biomolecules. 2020; 10(6). PMC: 7355836. DOI: 10.3390/biom10060834. View

14.

Zheng M, Hu Y, Gou R, Li S, Nie X, Li X . Development of a seven-gene tumor immune microenvironment prognostic signature for high-risk grade III endometrial cancer. Mol Ther Oncolytics. 2021; 22:294-306. PMC: 8426172. DOI: 10.1016/j.omto.2021.07.002. View

15.

Zeng Q, Liu Y, Liu J, Han J, Guo J, Lu S . Inhibition of ZIP4 reverses epithelial-to-mesenchymal transition and enhances the radiosensitivity in human nasopharyngeal carcinoma cells. Cell Death Dis. 2019; 10(8):588. PMC: 6683154. DOI: 10.1038/s41419-019-1807-7. View

16.

Yang H, Kong W, He L, Zhao J, ODonnell J, Wang J . MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res. 2008; 68(2):425-33. DOI: 10.1158/0008-5472.CAN-07-2488. View

17.

Peralta R, Xie B, Lontos K, Nieves-Rosado H, Spahr K, Joshi S . Dysfunction of exhausted T cells is enforced by MCT11-mediated lactate metabolism. Nat Immunol. 2024; 25(12):2297-2307. PMC: 11588660. DOI: 10.1038/s41590-024-01999-3. View

18.

Zhu X, Shen H, Yin X, Yang M, Wei H, Chen Q . Macrophages derived exosomes deliver miR-223 to epithelial ovarian cancer cells to elicit a chemoresistant phenotype. J Exp Clin Cancer Res. 2019; 38(1):81. PMC: 6377760. DOI: 10.1186/s13046-019-1095-1. View

19.

Feng Y, Tang Q, Wang B, Yang Q, Zhang Y, Lei L . Targeting the tumor microenvironment with biomaterials for enhanced immunotherapeutic efficacy. J Nanobiotechnology. 2024; 22(1):737. PMC: 11603847. DOI: 10.1186/s12951-024-03005-2. View

20.

Xiong J, Wu M, Chen J, Liu Y, Chen Y, Fan G . Cancer-Erythrocyte Hybrid Membrane-Camouflaged Magnetic Nanoparticles with Enhanced Photothermal-Immunotherapy for Ovarian Cancer. ACS Nano. 2021; 15(12):19756-19770. DOI: 10.1021/acsnano.1c07180. View