Improving immune checkpoint inhibitors' anti-tumor response and minimizing side effects

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Improving immunecheckpointinhibitors' anti-tumor response and minimizing side effects tohoku_univ

can sometimes use these checkpoints to escape detection. ICB is a powerful immunotherapy that works to block these checkpoints and bolsters the immune system's natural ability to fight cancer, rather than targeting the cancer directly.

The researchers tested their hypothesis by using anti-CTLA4—a widely used ICI—on laboratory mice with lymph node and distant metastases. Their findings confirmed that delivering CTLA4 blockers directly to tumor-positive lymph nodes elicited a potent anti-tumor response against local and systemic metastases, prolonging the mice's chance of survival.

The cancer immunotherapeutic effect was mediated by an upregulation of functionally active T cell population in the tumor-positive lymph node and spleen. In comparison, non-specific CTLA4 blockades elicited a weaker anti-tumor effect and exacerbated the side effects of using"Our findings are significant because they provide a simple approach to enhancing the efficacy of ICB, while minimizing its associated side effects," said Kodama.

Looking ahead, the team plans to further investigate lymphatic targeted approaches for improvement of therapeutic response in clinical trials to confirm its efficacy in humans.Metastatic lymph node targeted CTLA4 blockade: a potent intervention for local and distant metastases with minimal ICI-induced pneumonia,

 

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