Potential Novel Ovarian Cancer Treatment Targeting Myeloid-Derived Suppressor Cells

Abstract

Diagnosis by biopsy is difficult in the ovary since it is located deep in the abdomen. As a result, ovarian cancer is mostly found insidiously during exploratory laparotomy. Consequently, the early diagnosis of ovarian cancer is often difficult. The likelihood of peritoneal dissemination increases with the progress of ovarian cancer. With further progression, ovarian cancer metastasizes to the momentum, retroperitoneal lymph nodes, large intestine, small intestine, diaphragm, spleen, and other organs. Ovarian cancer has been considered a tumor that has a favorable response to chemotherapy, but more effective treatments are still being explored. Tumors use their own immune escape mechanism to evade host immunity. The immune checkpoint (IC) mechanism, one of the immune escape mechanisms, is established by programmed cell death-1 (PD-1)/PD-ligand-1 (PD-L1) communication. It has been shown that inhibiting PD-1/PD-L1 communication in various malignancies produces antitumor effects. However, the antitumor effect of ICI monotherapy on ovarian cancer is limited in actual clinical practice. In this review, we describe a novel cancer immunotherapeutic agent that targets myeloid-derived suppressor cells (MDSCs).

Keywords:

• Ovarian cancer
• anti-VEGF
• anti-GM-CSF
• MDSC
• CTL

Acknowledgment

The authors thank Professor Richard A. Young (Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA) for his research assistance.

Author contributions

K.A., T.H., and K.Y. performed most of the experiments and coordinated the project; K.A., T.H., and K.Y. conceived the study and wrote the manuscript. M.M. carefully reviewed this manuscript and reviewed medical science. I.K. provided information on clinical medicine and supervised the entire study.

Disclosure statement

The authors declare no potential conflicts of interest. The funders had no role in study design, data collection, and analysis; decision to publish; or preparation of the manuscript. The material (manuscript and figure) is original research, has not been previously published and has not been submitted for publication elsewhere while under consideration.

Additional information

Funding

This study was supported in part by grants from the Japan Ministry of Education, Culture, Science and Technology [24592510, 15K1079, and 19K09840], the Foundation of Osaka Cancer Research, The Ichiro Kanehara Foundation for the Promotion of Medical Science and Medical Care, the Foundation for Promotion of Cancer Research, the Kanzawa Medical Research Foundation. The Shinshu Medical Foundation, and the Takeda Foundation for Medical Science.