Effective low-dose Anlotinib induces long-term tumor vascular normalization and improves anti-PD-1 therapy

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Anlotinib, a multitarget tyrosine kinase inhibitor, shows efficacy in monotherapy for tumor angiogenesis.
• Combining Anlotinib with immune checkpoint inhibitors (ICIs) may optimize antitumor effects but requires clarification regarding dosage and side effects.

Purpose of the Study:

• To investigate the optimal dosage of Anlotinib when combined with anti-PD-1 therapy for enhanced antitumor efficacy and reduced toxicity.
• To elucidate the mechanisms underlying the combination therapy's effects on tumor vasculature and the tumor microenvironment.

Main Methods:

• Utilized effective low-dose Anlotinib in combination with anti-PD-1 therapy in preclinical models.
• Assessed tumor growth inhibition, vascular normalization, and immune cell infiltration (CD4+, CD8+ T cells, NK cells).
• Evaluated the role of interferon-gamma and CD8+ T cells in mediating antitumor responses.

Main Results:

• Effective low-dose Anlotinib inhibited tumor growth and reduced side effects compared to high doses.
• The combination therapy induced durable tumor vascular normalization and enhanced anti-PD-1 efficacy.
• Mechanistically, combination therapy increased intratumoral CD4+, CD8+ T, and NK cells, with CD8+ T cells being crucial for tumor suppression.

Conclusions:

• Combining effective low-dose Anlotinib with PD-1 blockade provides durable antitumor effects with improved safety.
• Employing an effective low dose of Anlotinib in combination with ICIs is more efficacious and safer than using tolerable high doses.