Immune checkpoint inhibitors’ anti-tumor response improvement and minimizing side effects

Scientists at Tohoku University have discovered a novel approach that improves the efficacy of immune checkpoint blockade (ICB) - a novel form of cancer treatment utilizing immune checkpoint inhibitors (ICIs) - and minimizes the associated side effects. They demonstrated that using ICIs to target tumor-positive lymph nodes generates a robust anti-tumor response against both local and systemic metastases.

The research team hypothesized that metastatic lymph node-targeted ICB could improve the anti-tumor response while uncoupling it from irAEs.

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 functionally4 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 immune checkpoint inhibitors, particularly interstitial pneumonia.

Reference:

Journal of Experimental & Clinical Cancer Research,DOI 10.1186/s13046-023-02645-w