Finally, the validation of the potential of CXCR4 blockade to counteract MICs immune escape may be challenging in vivo. Since CXCR4 is wildly expressed both by tumor and stroma/immune cells, the systemic delivery of CXCR4 inhibitors in vivo could affect these different cell subsets, impairing the possibility to finely dissect the players involved in the generation of the immunosuppressive microenvironment and the impact of CXCR4 inhibition on this tumor-stromal crosstalk. Here, CXCR4 is linked to neoplasm.