Homeostatic chemokines guide lymphoma cells to tumor growth-promoting niches within secondary lymphoid organs

The interaction between lymphoid tumor cells and their tissue microenvironment is thought to promote dissemination and progression of lymphoma. Those type of interactions consists of at least three cornerstones, among them mesenchymal- or bone marrow-derived stromal cells, cells of the innate or adaptive immune response, and the lymphoma cells themselves. The molecular pathways of crosstalk between the lymphoma cells and their nursing stroma are not well understood and their dissection is challenging because of (1) the complexity of stroma cell subpopulations, (2) kinetic and developmental transitions/switches of stroma composition, and (3) inherent technical difficulties to isolate and analyze defined stroma cell subsets. However, recent studies of bone marrow stroma interaction with leukemia or lymphoma cells have revealed therapeutic targets involved in regulating tumor cell mobilization. Release of tumor cells from their supportive niches could be effectuated by inhibition of homing and retention signals. The present review focuses on the effects of homing receptors and cytokines attributed to lymphoid tissue formation in tumor-stroma interactions within secondary lymphoid tissues. We discuss possible cellular and molecular mechanisms of lymphoma-stroma crosstalk and highlight novel therapeutic strategies based on the disruption of tumor-stroma interaction in secondary lymphoid organs.