Figure 2.

Hypothetical model of B-cell/MP interactions in B-cell lymphomas. This model predicts that indolent and retransformed or non-transformed lymphoma cells do not initially exhibit autonomous or spontaneous-independent neoplastic cell growth but instead must undergo interactions with indigenous non-neoplastic cells, specifically, monocytes or macrophages (MP)-derived tumor-associated MPs (TAMs) that bind, stimulate, and activate targeted lymphoma cells, to adopt aggressive autonomous phenotypes. The postulated mechanism for this relationship is that a high monocyte count is a surrogate biomarker for the tumor microenvironment, reflecting the functions of immunosuppressive peripheral blood monocytes recruited by lymphoma cells to differentiate monocytes into polarized MPs (M2) that can in turn activate the tumor cells. In addition, the aggregated TAMs (red) can protect tumor cells and, potentially, cancer stem cells (blue) within their clusters from chemotherapy, enabling the tumor cells to survive (residual disease) and re-establish (relapse) at a later time.