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

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.

Dendritic Cell Vaccines: A Promising Approach in the Fight against Ovarian Cancer.

Ovarian cancer (OC) is the deadliest gynecological malignancy in developed countries and is the seventh-highest cause of death in women diagnosed with cancer worldwide. Currently, several therapies are in use against OC, including debulking surgery, chemotherapy, as well as targeted therapies. Even though the current standard-of-care therapies improve survival, a vast majority of OC patients relapse. Additionally, immunotherapies have only resulted in meager patient outcomes, potentially owing to the intricate immunosuppressive nexus within the tumor microenvironment. In this scenario, dendritic cell (DC) vaccination could serve as a potential addition to the therapeutic options available against OC. In this review, we provide an overview of current therapies in OC, focusing on immunotherapies. Next, we highlight the potential of using DC vaccines in OC by underscoring the different DC subsets and their functions in OC. Finally, we provide an overview of the advances and pitfalls of current DC vaccine strategies in OC while providing future perspectives that could improve patient outcomes.

Systemic Reprogramming of Monocytes in Cancer.

Monocytes influence multiple aspects of tumor progression, including antitumor immunity, angiogenesis, and metastasis, primarily by infiltrating tumors, and differentiating into tumor-associated macrophages. Emerging evidence suggests that the tumor-induced systemic environment influences the development and phenotype of monocytes before their arrival to the tumor site. As a result, circulating monocytes show functional alterations in cancer, such as the acquisition of immunosuppressive activity and reduced responsiveness to inflammatory stimuli. In this review, we summarize available evidence about cancer-induced changes in monopoiesis and its impact on the abundance and function of monocytes in the periphery. In addition, we describe the phenotypical alterations observed in tumor-educated peripheral blood monocytes and highlight crucial gaps in our knowledge about additional cellular functions that may be affected based on transcriptomic studies. We also highlight emerging therapeutic strategies that aim to reverse cancer-induced changes in monopoiesis and peripheral monocytes to inhibit tumor progression and improve therapy responses. Overall, we suggest that an in-depth understanding of systemic monocyte reprogramming will have implications for cancer immunotherapy and the development of clinical biomarkers.