Inside-Out of Complement in Cancer.

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• The complement system, crucial for microbial defense, is increasingly recognized for its complex role in cancer.
• While extracellular complement activation is well-studied in cancer, the significance of intracellular complement pathways remains largely unexplored.
• Emerging evidence suggests complement can paradoxically promote cancer progression by suppressing anti-tumor immunity.

Purpose of the Study:

• To review the multifaceted functions of the complement system in cancer.
• To explore the implications of both extracellular and intracellular complement activation in malignancy.
• To discuss the potential of complement as a therapeutic target and biomarker in cancer treatment.

Main Methods:

• Literature review of recent studies on complement in cancer.
• Analysis of extracellular and intracellular complement activation pathways.
• Examination of complement protein distribution in tumor microenvironments and periphery.

Main Results:

• Complement can accelerate cancer progression, partly by suppressing anti-tumor immunity via host cell regulation within the tumor microenvironment.
• Intracellular complement activation, termed the 'complosome,' is vital for immune cell survival and T cell activation, suggesting a role in tumor cell survival and anti-tumor responses.
• Complement proteins exhibit distinct spatial distributions in tumors and peripheral tissues, influencing their functions.

Conclusions:

• The complement system's role in cancer is complex, involving both pro-tumor and anti-tumor effects.
• Intracellular complement activation presents a novel area of investigation with potential implications for tumor cell survival and anti-tumor immunity.
• Further research into complement pathways, including intracellular activation, is warranted to explore its potential as a biomarker and therapeutic target in oncology.