Table Info

Table 2.

Effect of XPO1 inhibition on immune cell function

Immune cell type	Effect on function	References
Myeloid cells	Depletes 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 cells	Reduces 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 cells	Increases splenic NK cell abundance and does not alter numbers in the TME in murine models.	[58, 72]
NK cells	Increases NK cell-mediated lysis of tumour cells and ADCC due to downregulation of HLA-E on malignant B cells.	[61, 62]
Neutrophils	Neutropenia has been reported in patients.	[63]
Neutrophils	Impairs extracellular trap formation.	[64]
B cells	Initial reduction of B cells in the bone marrow in mice, which recovers during prolonged treatment.	[72]
B cells	Minimal effect on antibody production or class switching.	[72]

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

Declarations

Author contributions

JGF: Conceptualization, Writing—original draft, Writing—review & editing. LGB: Writing—review & editing. TK: Writing—review & editing. CJW: Writing—review & editing. SIK: Writing—review & editing. MDB: Conceptualization, Writing—review & editing, Supervision. All authors read and approved the submitted version.

Conflicts of interest

TK and CJW are employees and stockholders of Karyopharm Therapeutics. All the other authors declare no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This work was supported by Karyopharm Therapeutics and the John Goldman Fellowship Follow-up Award from Leukaemia UK (to MDB). Karyopharm Therapeutics reviewed the manuscript for scientific accuracy prior to submission but had no role in study design, data collection, analysis, interpretation, or writing of the manuscript; the other provider of funds had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

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