IL10RB expression in cancer cells is associated with evolutionary changes to solidify treatment resistance.

BACKGROUND: Many molecular mechanisms underlying tumor escape, in which cancer cells undergo epithelial-to-mesenchymal transition (EMT) and thereby acquire metastatic potential and cancer stemness, have been reported. However, cancer metastasis and treatment resistance remain unconquerable for many cancer patients, probably due to diverse evolutionary changes in cancer cells. METHODS: Gene expressions in cancer cells with/without EMT-governing snail overexpression were compared using GeneChip microarray, and a gene was identified that was significantly increased with snail expression. The molecular functions were analyzed in vitro and in vivo using cancer cells overexpressing the identified gene, and the therapeutic efficacy induced by blocking the molecule was evaluated using mouse tumor models. RESULTS: Snail expression dramatically enhanced IL10RB expression in cancer cells, and IL10RB overexpression in cancer cells enhanced cellular adhesion, invasiveness, and chemoresistance. Treatment with anti-IL10RB blocking mAb attenuated such refractory properties of the IL10RB(+) tumor cells, and induced potent anti-tumor immunity in mouse tumor models. Combining anti-IL10RB and anti-PD1 therapy has a synergistic effect on tumor disappearance and improved prognosis. CONCLUSION: This study revealed that IL10RB is a key molecule in cancer intractability after achieving snail-induced EMT. Targeting IL10RB may be a promising strategy for improving clinical outcomes in the treatment of cancer.