Scientists at Tohoku University in Japan have devised a new approach to increase the efficacy of immune checkpoint blockade (ICB) – a new form of cancer treatment that uses immune checkpoint inhibitors (ICI) – while minimizing the associated side effects.
They demonstrated that using ICI to target tumor-positive lymph nodes resulted in a potent anti-tumor response against local and systemic metastases.
This study was published in the Journal of Experimental and Clinical Cancer Research.
The immune system uses ‘checkpoint proteins’ to regulate and control immune cell activity. But cancer cells can sometimes use these checkpoints to evade detection. ICB is a powerful immunotherapy that works to block these checkpoints and strengthen the immune system’s natural ability to fight cancer, rather than targeting cancer directly.
However, the efficacy of ICB treatment varies from person to person, and can be accompanied by some serious side effects. These are known as immune-related side effects (irAEs).
The research team, led by Tetsuya Kodama of Tohoku University’s Graduate School of Biomedical Engineering, hypothesized that ICBs targeted at metastatic lymph nodes could enhance the anti-tumor response while releasing them from iraEs.
The researchers tested their hypothesis by using anti-CTLA4 – a widely used ICI – in laboratory mice with lymph nodes and distant metastases. Their findings confirmed that delivering a CTLA4 blocker directly to tumor-positive lymph nodes elicited a potent anti-tumor response against local and systemic metastases, extending the mouse’s chance of survival.
The effects of cancer immunotherapy are mediated by upregulation of functionally active T-cell populations in tumor-positive lymph nodes and spleen. In comparison, non-specific CTLA4 blockade elicited a weaker anti-tumor effect and exacerbated the adverse effects of immune checkpoint inhibitors, particularly interstitial pneumonia.
“Our findings are significant because they provide a simple approach to enhance ICB efficacy, while minimizing the associated side effects,” said Kodama.
“Targeting tumor-positive lymph nodes with ICB can amplify the anti-tumor response and minimize irAE, leading to better outcomes for cancer patients.”
Going forward, the team plans to further investigate lymphatic-targeted approaches for enhancing therapeutic response in clinical trials to confirm their efficacy in humans.