You have full access to this open access article. Bone marrow mesenchymal stromal cells MSCs have been described as potent regulators of T-cell function, though whether they could impede the effectiveness of immunotherapy against acute myeloid leukemia AML is still under investigation. We examine whether they could interfere with the activity of leukemia-specific clonal cytotoxic T-lymphocytes CTLs and chimeric antigen receptor CAR T cells, as well as whether the immunomodulatory properties of MSCs could be associated with the induction of T-cell senescence.
Abrogated T cells were shown to retain their cytolytic activity. In summary, we show that MSCs are potent modulators of anti-leukemic T cells, and targeting their modes of action would likely be beneficial in a combinatorial approach with AML-directed immunotherapy.
Acute myeloid leukemia AML is a form of hematological cancer derived from the abnormal expansion of myeloid precursor cells, resulting in invasion of the bone marrow and ultimately failure of normal hematopoiesis. Chimeric antigen receptor CAR T cells are a promising avenue currently in early clinical trials [ 1 ]. In addition to immunosuppressive pathways intrinsic to AML blasts, neighboring constituents of the bone marrow can provide additional protection.
In particular, a lot of interest has been garnered for resident mesenchymal stromal cells MSCs which were found to possess an impressive immunomodulatory capacity in suppressing the proliferation and the inflammatory potential of T cells [ 5 ].
This along with other properties such as multipotency has highlighted the therapeutic potential of MSCs in regenerative medicine and the treatment of immune disorders [ 6 ]. It follows to ask if MSCs can interfere with the action of T-cell-based immunotherapies in the context of hematological malignancy. At the time of writing, few reports have come out addressing this topic. More recently, it was reported that infusion of MSCs did not affect CD19 CAR T-cell activity in acute lymphocytic leukemia xenografts despite being able to efficiently control inflammation in a acute colitis murine model [ 8 ].
