ADAMTS proteases and the tumor immune microenvironment: Lessons from substrates and pathologies

Area of Science:

• Biochemistry
• Immunology
• Molecular Biology

Background:

• ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) proteases have long been associated with inflammatory processes.
• While their functions are increasingly understood, many aspects of their roles in inflammation and immunity remain unclear.

Purpose of the Study:

• To review key studies on ADAMTS proteases and their substrates in inflammatory and immune responses.
• To update knowledge on ADAMTS involvement in cancer, particularly within the tumor immune microenvironment.
• To discuss the ongoing debate regarding the specific activities of intact versus cleaved ADAMTS proteins in inflammation.

Main Methods:

• Literature review of studies on ADAMTS proteases and their substrates.
• Focus on non-oncological inflammatory and immune disorders.
• Inclusion of recent findings on cancer and the tumor immune microenvironment.

Main Results:

• ADAMTS proteases play significant roles in both non-oncological inflammatory conditions and the tumor immune microenvironment.
• The precise functions of intact ADAMTS proteins versus their cleaved fragments in inflammation are still under investigation.
• Evidence suggests ADAMTS proteases influence immune cell function and extracellular matrix remodeling.

Conclusions:

• A comprehensive understanding of ADAMTS protease activities is essential for elucidating their contribution to immune phenotypes.
• Further research into ADAMTS proteases may reveal new therapeutic strategies and diagnostic markers for inflammatory diseases and cancer.
• Clarifying the dual roles of ADAMTS proteases and their fragments could lead to targeted interventions.