Recent studies also highlight the impact of tumor type on the local tissue microenvironment, with IDH1 mutant gliomas being associated with more profound immune suppression, compared with brain metastases which are populated with relatively more lymphocytes.22,23 In addition to the anatomical restrictions that impede T-cell trafficking to brain tumor parenchyma, bone marrow sequestration of lymphocytes in bone marrow was also shown to impair tumor infiltration in GBMs as a result of tumor-imposed internalization of the S1P receptor, S1P1, on T cells.51 Here, S1PR1 is linked to neoplasm.