Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Nov 5;10(11):2826.
doi: 10.3390/biomedicines10112826.

The Role of TIM-3 and LAG-3 in the Microenvironment and Immunotherapy of Ovarian Cancer

Mateusz Kozłowski  1 , Dominika Borzyszkowska  1 , Aneta Cymbaluk-Płoska  1
Affiliations
Review

The Role of TIM-3 and LAG-3 in the Microenvironment and Immunotherapy of Ovarian Cancer

Mateusz Kozłowski et al. Biomedicines. .

Abstract

Ovarian cancer has the highest mortality rate among gynecologic malignancies. The main treatment options are surgical removal of the tumor and chemotherapy. Cancer treatment has been revolutionized by immunotherapy, which has developed explosively over the past two decades. Clinical anticancer strategies used in immunotherapy include therapies based on the inhibition of PD-1, PD-L1 or CTLA-4. Despite encouraging results, a large proportion of cancer patients are resistant to these therapies or eventually develop resistance. It is important to perform research that will focus on immunotherapy based on other immune checkpoint inhibitors. The aim of the review was to analyze studies considering the expression of TIM-3 and LAG-3 in the ovarian cancer microenvironment and considering immunotherapy for ovarian cancer that includes antibodies directed against TIM-3 and LAG-3. As the data showed, the expression of the described immune checkpoints was shown in different ways. Higher TIM-3 expression was associated with a more advanced tumor stage. Both TIM-3 and LAG-3 were co-expressed with PD-1 in a large proportion of studies. The effect of LAG-3 expression on progression-free survival and/or overall survival is inconclusive and certainly requires further study. Co-expression of immune checkpoints prompts combination therapies using anti-LAG-3 or anti-TIM-3. Research on immune checkpoints, especially TIM-3 and LAG-3, should be further developed.

Keywords: LAG-3; TIM-3; immune checkpoint; immune checkpoint inhibition; immunotherapy; microenvironment; ovarian cancer.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Immune checkpoints with indication of described molecules.
Figure 2
Figure 2
The importance of TIM-3 and LAG-3 expression in the microenvironment and immunotherapy.
See this image and copyright information in PMC

References

    1. Ye S., Chen W., Zheng Y., Wu Y., Xiang L., Li T., Yang H. Peripheral lymphocyte populations in ovarian cancer patients and correlations with clinicopathological features. J. Ovarian Res. 2022;15:43. doi: 10.1186/s13048-022-00977-3. - DOI - PMC - PubMed
    1. Stewart C., Ralyea C., Lockwood S. Ovarian Cancer: An Integrated Review. Semin. Oncol. Nursing. 2019;35:151–156. doi: 10.1016/j.soncn.2019.02.001. - DOI - PubMed
    1. Akter S., Rahman M.A., Hasan M.N., Akhter H., Noor P., Islam R., Kim S.S. Recent Advances in Ovarian Cancer: Therapeutic Strategies, Potential Biomarkers, and Technological Improvements. Cells. 2022;11:650. doi: 10.3390/cells11040650. - DOI - PMC - PubMed
    1. Cancer Stat Facts: Ovarian Cancer. [(accessed on 27 September 2022)]; Available online: https://seer.cancer.gov/statfacts/html/ovary.html.
    1. Yang C., Xia B.R., Zhang Z.C., Zhang Y.J., Lou G., Jin W.L. Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant. Front. Immunol. 2020;11:577869. doi: 10.3389/fimmu.2020.577869. - DOI - PMC - PubMed