TAB2 Promotes Immune Escape and Chemoresistance Through NF‐κB Pathway Activation in Cervical Cancer

TL;DR

TAB2 helps cervical cancer cells resist chemotherapy and avoid immune detection by activating the NF-κB pathway, making it a potential target for treatment.

Contribution

TAB2 is identified as a novel regulator of chemoresistance and immune escape in cervical cancer via NF-κB pathway activation.

Findings

TAB2 overexpression increases chemoresistance and immune escape in cervical cancer cells.

Inhibiting TAB2 or the NF-κB pathway restores sensitivity to cisplatin and enhances immune cell killing.

Restoring PD-L1 expression rescues the resistant phenotype in TAB2-depleted cells.

Abstract

Cervical cancer (CC) remains a major health challenge with high mortality rates due to chemoresistance and immune escape. However, the underlying mechanisms remain unclear. We investigated the role of TAB2 in CC using cisplatin‐resistant and parental cell lines. Cell proliferation, migration, sphere formation and T cell‐mediated killing assays were performed. Western blot and qRT‐PCR analysed protein and mRNA expression. NF‐κB pathway involvement was examined using the BAY 11–7082 inhibitor. TAB2 expression was significantly elevated in cisplatin‐resistant CC cells. TAB2 overexpression promoted chemoresistance and immune escape through NF‐κB pathway activation. Conversely, TAB2 knockdown or NF‐κB inhibition sensitised resistant cells to cisplatin and enhanced T cell‐mediated killing. The resistant phenotype could be rescued by restoring PD‐L1 expression. Our findings reveal TAB2 as a critical regulator of both chemoresistance and immune escape in CC through NF‐κB pathway activation. This suggests TAB2 as a potential therapeutic target for overcoming treatment resistance in CC.

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