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Cancer research

Targeting the PI3K/Akt Pathway to Overcome Resistance to Cancer Immunotherapy

Strategic Insights

— 2 min read

Research at Chiba University in Japan has identified the PI3K/Akt signaling pathway as a key regulator of CD155 expression, which contributes to resistance to cancer immunotherapy, particularly in tumors with an inflamed tumor microenvironment. The study found that inhibition of Dyrk1A, a key regulator of CD155 expression, or treatment with DYRK1A inhibitors effectively mitigated PD-1 blockade resistance. Additionally, cetuximab-mediated epidermal growth factor receptor blockade reduced CD155 expression by targeting downstream PI3K/Akt signaling in certain head and neck squamous cell carcinoma cell lines.

Key Takeaways:

  • The PI3K/Akt signaling pathway plays a crucial role in regulating CD155 expression, which is involved in resistance to cancer immunotherapy.
  • Inhibition of Dyrk1A or treatment with DYRK1A inhibitors effectively mitigated PD-1 blockade resistance in cancer cells.
  • Cetuximab-mediated epidermal growth factor receptor blockade reduced CD155 expression by targeting downstream PI3K/Akt signaling in certain head and neck squamous cell carcinoma cell lines.
  • High CD155 expression correlated with Akt phosphorylation, particularly impacting PD-1 blockade resistance in patients with head and neck squamous cell carcinoma (HNSCC).
  • The study suggests that targeting the PI3K/Akt pathway could overcome resistance to cancer immunotherapy, particularly in cancers with an inflamed tumor microenvironment and high CD155 expression.
  • The research identified Shusuke Kawashima and colleagues from Chiba University as the lead researchers, with contributions from Katsushige Kawase, Tatsuya Nishi, Takashi Inozume, Takao Morinaga, Masahito Kawazu, Toyoyuki Hanazawa, and Yosuke Togashi.
  • The study provides new evidence for the role of the PI3K/Akt pathway in regulating CD155 expression and its impact on cancer immunotherapy resistance.

Statistics:

  • 96 patients with HNSCC were included in the study, with CD155 expression correlated with Akt phosphorylation, particularly impacting PD-1 blockade resistance.
  • The research used CRISPR screening to identify dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) as one of the key regulators of CD155 expression.
  • The study found that the PI3K/Akt signaling pathway played a crucial role in regulating CD155 expression, particularly in cancers with an inflamed tumor microenvironment.
  • CD155 expression was significantly higher in cancers with high CD8+ T cell infiltration.

Sources:

  • NewsRx. Studies from Chiba University Yield New Information about Cancer (PI3K/Akt signaling pathway regulates CD155 expression involved in resistance to cancer immunotherapy). Immunotherapy Weekly. August 20, 2025; p 1262.
  • Amer Assoc Cancer Research. Cancer Immunology Research, 2025.
  • Cancer Immunology Research can be contacted at: Amer Assoc Cancer Research, 615 Chestnut St, 17TH Floor, Philadelphia, PA 19106-4404, USA.
  • Additional information may be obtained from Shusuke Kawashima, Chiba University, Chiba, Chiba, Japan.

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