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

Chie Kudo-Saito1, Hiroki Ozawa2, Hiroshi Imazeki2

  • 1Department of Immune Medicine, National Cancer Center Research Institute, Tokyo, Japan. ckudo@ncc.go.jp.

BJC Reports
|March 14, 2026
PubMed
Abstract

Insights

Interleukin-10 receptor subunit beta (IL10RB) drives cancer's resistance to treatment and metastasis after epithelial-to-mesenchymal transition (EMT). Targeting IL10RB with blocking antibodies shows promise for improving cancer treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Cancer cells can evade treatments through epithelial-to-mesenchymal transition (EMT), gaining metastatic potential and cancer stemness.
  • Despite known mechanisms, cancer metastasis and treatment resistance remain significant challenges due to cancer cell evolution.

Purpose of the Study:

  • To identify novel molecular mechanisms driving cancer intractability post-EMT.
  • To evaluate the therapeutic potential of targeting identified molecules in preclinical cancer models.

Main Methods:

  • Gene expression profiling using GeneChip microarray to compare cells with and without EMT-governing snail overexpression.
  • In vitro and in vivo functional analyses of the identified gene in cancer cells overexpressing it.
  • Evaluation of therapeutic efficacy using anti-IL10RB blocking monoclonal antibodies (mAbs) in mouse tumor models.

Main Results:

  • Snail overexpression significantly upregulated Interleukin-10 receptor subunit beta (IL10RB) expression in cancer cells.
  • IL10RB overexpression enhanced cancer cell adhesion, invasiveness, and chemoresistance.
  • Anti-IL10RB mAb treatment reduced tumor refractoriness and induced anti-tumor immunity; combination with anti-PD1 therapy led to synergistic tumor eradication.

Conclusions:

  • IL10RB is identified as a critical mediator of cancer intractability following snail-induced EMT.
  • Targeting IL10RB presents a promising therapeutic strategy to enhance clinical outcomes in cancer treatment.

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