Collagen and Its Roles in the Tumor Immune Microenvironment: Structure, Function, and Therapeutic Potential

Area of Science:

• Biochemistry
• Immunology
• Oncology

Background:

• Collagen is the main structural protein in the extracellular matrix, influencing the tumor immune microenvironment (TIME).
• Biomechanical changes in collagen, such as stiffening and altered fiber alignment, create migration tracks and impede immune cell infiltration.
• These collagen-mediated changes reinforce malignant behaviors and immune exclusion, contributing to immunotherapy resistance.

Purpose of the Study:

• To review the structural features, biological functions, and regulatory pathways of collagen within the TIME.
• To explore collagen's role in the tumor immune microenvironment and its implications for cancer progression and treatment.
• To identify potential therapeutic strategies targeting collagen to overcome immunotherapy resistance.

Main Methods:

• Literature review examining collagen's structural and functional roles in the TIME.
• Analysis of mechanosensing and mechanotransduction pathways involved in collagen's effects.
• Synthesis of current and future clinical strategies for targeting collagen in cancer therapy.

Main Results:

• Collagen alterations in the TIME, including stiffening and alignment, facilitate tumor cell migration and hinder immune cell infiltration.
• Mechanosensing pathways transduce biomechanical collagen cues, promoting malignant behavior and immune exclusion.
• Collagen's dynamic roles present it as a viable therapeutic target for enhancing immunotherapy outcomes.

Conclusions:

• Targeting collagen-associated mechanisms, such as fibrosis and receptor signaling, can potentially overcome immunotherapy resistance.
• Strategies include targeting cancer-associated fibroblasts, enzymatic or physical matrix remodeling, and inhibiting collagen receptor signaling.
• Future research should focus on biomarker-guided therapy, combining mechanobiology insights, and noninvasive monitoring for optimized immunotherapy.