Modulation of anti-tumour immunity by XPO1 inhibitors

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Exportin-1 (XPO1) is a key nuclear export protein implicated in cancer cell proliferation and survival.
• Overexpression or mutation of XPO1 is common in various cancers, making it a therapeutic target.
• Selective XPO1 inhibitors (XPO1i) are developed to inhibit cancer growth and induce apoptosis.

Purpose of the Study:

• To review the immunomodulatory effects of XPO1 inhibition.
• To explore the potential of combining XPO1 inhibitors with immunotherapy for enhanced cancer treatment.
• To discuss the role of XPO1 inhibition in sensitizing cancer cells to immune responses.

Main Methods:

• Literature review of studies on XPO1 inhibition and its effects on the tumor microenvironment.
• Analysis of evidence for XPO1i's impact on immune cells, including macrophages and myeloid-derived suppressor cells (MDSCs).
• Examination of XPO1i's influence on immune checkpoints and cancer cell susceptibility to T cell and NK cell activity.

Main Results:

• XPO1 inhibition exhibits immunomodulatory properties beyond direct anti-cancer effects.
• XPO1i can skew macrophage polarization, inhibit neutrophil extracellular traps, and modulate immune checkpoint expression.
• XPO1 inhibition blocks MDSCs and sensitizes cancer cells to T cell and NK cell-mediated killing.

Conclusions:

• XPO1 inhibition, exemplified by selinexor, possesses significant immunomodulatory capabilities.
• Combining XPO1 inhibitors with immunotherapies presents a promising strategy to improve cancer treatment efficacy.
• Further clinical trials are warranted to evaluate selinexor in combination with various immunotherapeutic approaches.