TIM3 Checkpoint Inhibition Fails to Prolong Survival in OvarianCancer-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 OvarianCancer-Bearing Mice

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

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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.

Original language	English
Article number	1147
Pages (from-to)	1-18
Number of pages	18
Journal	Cancers
Volume	16
Issue number	6
DOIs	https://doi.org/10.3390/cancers16061147
Publication status	Published - 14 Mar 2024

Bibliographical note

Funding Information:
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.).

Publisher Copyright:
© 2024 by the authors.

Keywords

checkpoint inhibitor; ovarian cancer; chemotherapy; preclinical

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109594749Final published version, 4.56 MBLicence: CC BY

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title = "TIM3 Checkpoint Inhibition Fails to Prolong Survival in OvarianCancer-Bearing Mice",

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. ",

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note = "Funding Information: 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.). Publisher Copyright: {\textcopyright} 2024 by the authors.",

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AU - Berckmans, Yani

AU - Vankerckhoven, Ann

AU - Caro, Aarushi Audhut

AU - Kempeneers, Julie

AU - Ceusters, Jolien

AU - Thirion, Gitte

AU - Vandenbrande, Katja

AU - Vergote, Ignace

AU - Laoui, Damya

AU - Coosemans, An

N1 - Funding Information: 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.). Publisher Copyright: © 2024 by the authors.

PY - 2024/3/14

Y1 - 2024/3/14

N2 - 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.

AB - 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.

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ER -

TIM3 Checkpoint Inhibition Fails to Prolong Survival in OvarianCancer-Bearing Mice

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