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

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.