Remodeling of Metastatic Vasculature Reduces Lung Colonization and Sensitizes Overt Metastases to Immunotherapy

Area of Science:

• Oncology
• Vascular Biology
• Immunotherapy

Background:

• Metastases are the leading cause of cancer mortality due to limited effective therapies.
• Targeting tumor vasculature and the pre-metastatic niche presents a therapeutic opportunity.

Purpose of the Study:

• To evaluate the efficacy of a fusion compound, cytokine LIGHT and vascular targeting peptide (LIGHT-VTP), in preventing and treating cancer metastases.
• To investigate LIGHT-VTP's impact on tumor vasculature, pre-metastatic niche, and immune cell infiltration.

Main Methods:

• Administration of LIGHT-VTP in mouse models of lung cancer and melanoma.
• Assessment of tumor vascularization, intravasation, metastatic colonization, and immune cell populations (GrzB+ T cells).
• Evaluation of sensitization to anti-PD-1 checkpoint inhibitors.

Main Results:

• LIGHT-VTP normalized tumor vasculature, preventing cancer cell intravasation in primary lung cancer.
• It targeted pre-metastatic niches, reducing hyper-permeability and ECM deposition, thereby blocking lung colonization.
• LIGHT-VTP normalized vasculature in melanoma metastases, increased effector T cells, and induced features that sensitized metastases to anti-PD-1 therapy.

Conclusions:

• LIGHT-VTP is a promising therapeutic agent for preventing metastatic development.
• It demonstrates anti-tumor effects in established metastases and enhances the efficacy of checkpoint inhibitors.