Cancer dormancy-related changes in immune checkpoint molecules and the role of autophagy

Recurrence or relapse of cancer is very critical in the progression of the disease and related deaths. It is caused by metastasis, immune response and drug resistance-related mechanisms. Cancer cell dormancy emerges as an important determinant of cancer recurrence. Immune surveillance is one of the mechanisms that limits the number of dormant cancer foci. Therefore, understanding the mechanisms of interaction between dormant cells and components of the immune system is of great importance. Moreover, the role of autophagy in this context is not clear. In this study, 2D and 3D cancer models of dormancy have been developed and characterized, and co-culture systems with immune cells have been established. Using these models and systems, a set of immune checkpoint molecules that are differentially regulated in dormant cancer cells compared to proliferative counterparts, have been identified. We focused on one of the immune checkpoint genes/proteins that were differentially expressed in dormant cancer cells compared to actively proliferating counterparts. We also analyzed the role of autophagy in dormancy-related immune checkpoint responses. Our study underlines the importance of less studied immune checkpoint molecules and autophagy in dormant cancer-immune cell interactions, affecting anti-cancer immune responses. The study provides a battery of drug targets for the development of novel anti-cancer and anti-dormancy immune checkpoint inhibitors.