TIM3 Checkpoint Inhibition Fails to Prolong Survival in Ovarian Cancer-Bearing Mice

Yani Berckmans; Ann Vankerckhoven; Aarushi Audhut Caro; Julie Kempeneers; Jolien Ceusters; Gitte Thirion; Katja Vandenbrande; Ignace Vergote; Damya Laoui; An Coosemans

doi:10.3390/cancers16061147

TIM3 Checkpoint Inhibition Fails to Prolong Survival in Ovarian Cancer-Bearing Mice

Cancers (Basel). 2024 Mar 14;16(6):1147. doi: 10.3390/cancers16061147.

Authors

Yani Berckmans¹, Ann Vankerckhoven¹, Aarushi Audhut Caro^{1

2

3}, Julie Kempeneers^{1

4}, Jolien Ceusters¹, Gitte Thirion¹, Katja Vandenbrande¹, Ignace Vergote⁴, Damya Laoui^{2

3}, An Coosemans¹

Affiliations

¹ Laboratory of Tumor Immunology and Immunotherapy, Department of Oncology, Leuven Cancer Institute, KU Leuven, 3000 Leuven, Belgium.
² Laboratory of Dendritic Cell Biology and Cancer Immunotherapy, VIB Center for Inflammation Research, 1050 Brussels, Belgium.
³ Brussels Center for Immunology, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
⁴ Department of Gynaecology and Obstetrics, Leuven Cancer Institute, University Hospitals Leuven, 3000 Leuven, Belgium.

Abstract

Immune checkpoint inhibitor (ICI) therapy has proven revolutionary in the treatment of some cancers. However, ovarian cancer remains unresponsive to current leading ICIs, such as anti-PD1 or anti-PD-L1. In this article, we explored the potential of an upcoming checkpoint molecule, T-cell immunoglobulin and mucin domain 3 (TIM3), for the treatment of ovarian cancer using a syngeneic orthotopic mouse model (ID8-fLuc). Besides therapeutic efficacy, we focused on exploring immune changes in tumor tissue and peritoneal fluid. Our results showed no improvement in survival in ovarian cancer-bearing mice after anti-TIM3 treatment when used as monotherapy nor when combined with anti-PD1 or standard-of-care chemotherapy (carboplatin/paclitaxel). This was reflected in the unaltered immune infiltration in treated mice compared to control mice. Altering the order of drug administration within the combination treatment altered the survival results, but did not result in a survival benefit over chemotherapy alone. These findings highlight the need for further preclinical studies to find beneficial treatment schemes and combination therapies for ovarian cancer.

Keywords: checkpoint inhibitor; chemotherapy; ovarian cancer; preclinical.

Grants and funding

D.L. is funded by grants of Vrije Universiteit Brussel, VIB, Kom op tegen kanker and Stichting tegen kanker. A.C. is funded by Vriendtjes tegen kanker and Kom op tegen kanker. This research was funded by Kom Op Tegen Kanker (Stand up to Cancer), the Flemish cancer society (2019/11955/1 to A.C.).