Research Paper|Volume 16, Issue 1|pp 207—225

Signatures of tumor-associated macrophages correlate with treatment response in ovarian cancer patients

Yang Gao^1,^2,³, Yuwen Qi^1,^2,³, Yin Shen⁴, Yaxing Zhang^1,^2,³, Dandan Wang^1,^2,³, Min Su^1,^2,³, Xuelian Liu^1,^2,³, Anjin Wang^1,^2,³, Wenwen Zhang^1,^2,³, Can He^1,^2,³, Junyuan Yang^1,^2,³, Mengyuan Dai^1,^2,³, Hua Wang^1,^2,³, Hongbing Cai^1,^2,³

¹Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China
²Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China
³Hubei Cancer Clinical Study Center, Wuhan, China
⁴Department of Integrative Ultrasound Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China

* Equal contribution and share first authorship

Received: June 27, 2023Accepted: November 2, 2023Published: January 3, 2024

https://doi.org/10.18632/aging.205362

Copyright: © 2024 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Ovarian cancer (OC) ranks as the second leading cause of death among gynecological cancers. Numerous studies have indicated a correlation between the tumor microenvironment (TME) and the clinical response to treatment in OC patients. Tumor-associated macrophages (TAMs), a crucial component of the TME, exert influence on invasion, metastasis, and recurrence in OC patients. To delve deeper into the role of TAMs in OC, this study conducted an extensive analysis of single-cell data from OC patients. The aim is to develop a new risk score (RS) to characterize the response to treatment in OC patients to inform clinical treatment. We first identified TAM-associated genes (TAMGs) in OC patients and examined the protein and mRNA expression levels of TAMGs by Western blot and PCR experiments. Additionally, a scoring system for TAMGs was constructed, successfully categorizing patients into high and low RS subgroups. Remarkably, significant disparities were observed in immune cell infiltration and immunotherapy response between the high and low RS subgroups. The findings revealed that patients in the high RS group had a poorer prognosis but displayed greater sensitivity to immunotherapy. Another important finding was that patients in the high RS subgroup had a higher IC50 for chemotherapeutic agents. Furthermore, further experimental investigations led to the discovery that THEMIS2 could serve as a potential target in OC patients and is associated with EMT (epithelial-mesenchymal transition). Overall, the TAMGs-based scoring system holds promise for screening patients who would benefit from therapy and provides valuable information for the clinical treatment of OC.