Cross-Talk Between Cancer Cells And Immune Cells

Introduction

In the last few years immunotherapy has emerged as an effective treatment to cancer together with chemotherapy, radiation and surgery. The basic idea is to enforce and engineer the immune system to fight cancer. The most prevalent approaches include blocking immune checkpoints to keep the immune system active, introducing T cells including T cells with chimeric antigen receptors to enhance specificity to malignant cells and monoclonal antibodies. Unfortunately, cancer cells can evade the immune system by reducing antigen presentation, affect immune cells location and induce suppression program.

In this project we aim to decipher the interactions between dendritic cells and ovarian cancer cells. Ovarian cancer is one of the most deadly types of cancer casing more than 10,000 death in the US every year. Dendritic cells is a bridge between the innate immune system and adaptive immune system. Beside phagocytic function, dendritic cells act as an antigen-presenting cells that can acquire antigens from malignant cells and activate effector T - cells in secondary lymphoid tissues or tumor draining lymph nodes and thus boost their cytotoxic function. Most of the tumors are infiltrated by dendritic cells but nevertheless not all of these tumors undergo killing by effector T – cells. We question how cancer cells and other tumor infiltrated cells render the activity and physiology of dendritic cells.

Materials and Methods

Co-culturing mice bone marrow – derived dendritic cells and ID8 cells, an epithelial ovarian cancer cell line, in the presence of modulating culture conditions and stimulation factors like IFN-b and LPS, we are examining changes in the expression patterns of dendritic cell`s surface molecules such as CD40, PDL1 and CD86 which is a co-stimulatory molecule crucial for T – cells activation and polarization.

Results and Discussion

As a result of such observations, it appears that the expression of CD86 is downregulated in the presence of malignant cells, while this suppression effect is eliminated in the case of incubating dendritic cells in the conditional media from ID8 cells. It would seem that direct cell-to-cell contact is important for such suppression. It would be interesting to check this evidence in more complex conditions in vivo using mouse model.

Conclusion

Understanding of interactions between dendritic cells and ID8 cells, how dendritic cells response to signals from malignant surroundings and how exactly ovarian cancer cells influence antigen - presentation will help us to find new targets for immunotherapy.