Endothelial cells in tumor microenvironment: insights and perspectives

Area of Science:

• Oncology
• Immunology
• Cell Biology

Background:

• The tumor microenvironment (TME) is a complex ecosystem comprising tumor cells, immune cells, endothelial cells (ECs), and extracellular matrix.
• Endothelial cells (ECs) play critical roles in regulating blood fluidity, permeability, tumor angiogenesis, and antitumor immune responses within the TME.
• Tumor-associated ECs exhibit distinct phenotypes and functions compared to normal ECs, often promoting tumor progression and immune suppression.

Purpose of the Study:

• To elucidate the multifaceted role of ECs in the TME.
• To explore the potential of targeting ECs for improving cancer therapy.
• To understand how ECs influence antitumor immunity and response to immunotherapies.

Main Methods:

• Phenotypic and functional characterization of tumor-associated ECs.
• Analysis of EC interactions with immune cells and tumor cells.
• Investigation of EC contributions to tertiary lymphoid structures (TLS).

Main Results:

• Tumor-associated ECs act as semi-professional antigen-presenting cells, influencing T cell priming and activation.
• Abnormal ECs in tumors promote immunosuppressive mechanisms, supporting tumor growth and metastasis.
• Tumor-associated ECs contribute to TLS formation, which correlates with improved responses to immune checkpoint inhibitors (ICI).

Conclusions:

• ECs are crucial regulators of the TME, impacting both angiogenesis and immune responses.
• Targeting tumor-associated ECs presents a viable strategy to enhance antitumor immunity and therapeutic outcomes.
• Combination therapies involving anti-angiogenic agents and immunotherapies aim to modulate ECs and immune cells for improved cancer treatment.