Macrophages and myeloid derived suppressor cells-independent dysregulation of thymopoiesis by CCL2 in acute myeloid leukemia

In cancer patients and experimental mouse models, the CCL2 chemokine is well known to directly stimulate the proliferation and migration of tumor cells. It also promotes their growth and metastasis through the recruitment of type 2 macrophages and myeloid derived suppressor cells that inhibit T-cell responses. Accumulation of CCL2 has been described in the sera of patients suffering from acute myeloid leukemia (AML), however, its functions in disease development remain to be determined. Using an AML experimental mouse model, we have recently demonstrated elevated levels of CCL2 in the sera and thymi of mice. CCL2 blockade in vivo resulted in prolonged leukemic mice survival, lower tumor burden and enhanced anti-leukemic responses. In this study we highlighted a surprising role of CCL2 during AML which affects thymic function in the absence of macrophages and myeloid derived suppressor cells recruitment.