From:  Modulation of anti-tumour immunity by XPO1 inhibitors
 

Effect of XPO1 inhibition on immune cell function

Immune cell typeEffect on functionReferences
Myeloid cellsDepletes lymphoma-associated macrophages.[54]
Reduces immunosuppressive effects of human MDSCs in a murine model of lymphoma.[56]
Macrophage polarisation from M2-like to M1-like within the TME.[55]
Increases macrophage abundance within the TME in murine models of pancreatic cancer.[57]
Increases MDSC infiltration in murine model of melanoma murine.[58]
T cellsReduces LAG-3, TIM-3 and PD-1 expression on tumour-infiltrating CD8+ T cells in murine models.
Unaltered regulatory T cell infiltration in murine tumour models.
Increased granzyme B and no induction of immune checkpoints in MM patient samples.
At high concentrations impairs TCR signaling and T cell proliferation.		[58, 72]
Pre-treatment of breast cancer cell lines enhances TRAIL-R2xCD3 bispecific antibody activity.[90]
Improves anti-CD19 CAR-T cell activity in vitro and in vivo.[105, 106]
NK cellsIncreases splenic NK cell abundance and does not alter numbers in the TME in murine models.[58, 72]
Increases NK cell-mediated lysis of tumour cells and ADCC due to downregulation of HLA-E on malignant B cells.[61, 62]
NeutrophilsNeutropenia has been reported in patients.[63]
Impairs extracellular trap formation.[64]
B cellsInitial reduction of B cells in the bone marrow in mice, which recovers during prolonged treatment.[72]
Minimal effect on antibody production or class switching.[72]
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MDSCs: myeloid-derived suppressor cells; TME: tumour microenvironment; LAG-3: lymphocyte activation gene-3; TIM-3: T-cell immunoglobulin and mucin-domain containing-3; PD-1: programmed cell death protein 1; TCR: T cell receptor; CAR: chimeric antigen receptor; NK: natural killer; ADCC: antibody-dependent cellular cytotoxicity; MM: multiple myeloma; XPO1: exportin-1; PD-1: programmed cell death protein 1; TRAIL: TNF-related apoptosis-inducing ligand