The tumor microenvironment (TME) is a complex environment composed of a variety of cell types including cancer cells, endothelial cells, and immune cells. Cross talk between the cells in TME plays a central role in tumor growth, progression, metastasis, and response to therapy. Coculture is a method to study the interaction between various types of cells in vitro and provides a way to mimic the in vivo conditions. Two or more types of cells can be cultured in a way that, they are in direct contact with each other (direct coculture) or, separated while still communicating through the secretion of soluble factors (indirect coculture). In this chapter, we focus on indirect coculture, specifically studying the modulation of immune cells by breast cancer lines through paracrine signaling. Cells are grown in transwells that allow the transfer of soluble factors but prevent cell-to-cell contact. This model helps us understand the effects of soluble factors on both immune cells and cancer cells.