Toll-like Receptors in Ovarian Cancer as Targets for Immunotherapies

Abstract

In the last decade, it has become apparent that toll-like receptor (TLR) signaling can play an important role in ovarian cancer (OC) progression. Interestingly, TLR activation in immune cells can help activate an anti-tumor response, while TLR signaling in tumor cells themselves is often associated with cancer-promoting inflammation. For example, it has been shown that TLR activation in dendritic cells can result in more effective antigen presentation to T cells, thereby favoring tumor eradication. However, aberrant TLR expression in OC cells is associated with more aggressive disease (likely due to recruitment of pro-tumoral leukocytes to the tumor site) and has also been implicated in resistance to mainstream chemotherapy. The delicate balance of TLR activation in the tumor microenvironment in different cell types altogether help shape the inflammatory profile and outcome of tumor growth or regression. With further studies, specific activation or repression of TLRs may be harnessed to offer novel immunotherapies or adjuvants to traditional chemotherapy for some OC patients. Herewith, we review recent literature on basic and translational research concerning therapeutic targeting of TLR pathways for the treatment of OC.

Keywords: immunotherapy; ovarian cancer; pattern-recognition receptors; toll-like receptors; tumor microenvironment.

Figure 1

Toll-like receptor (TLR) activation in ovarian cancer cells and immune cells results in differential effects on tumor progression. While TLR engagement in immune cells may facilitate an anti-tumor inflammatory microenvironment, their signaling pathways in tumor cells may result in immunosuppression and resistance to chemotherapy, thereby furthering tumor growth.