Tissue Injury and Biomaterial Treatment Modulate Tumor Growth and Response to Immunotherapy

Area of Science:

• Oncology
• Immunology
• Regenerative Medicine

Background:

• Immunotherapies, including immune checkpoint blockade (ICB), have revolutionized cancer treatment.
• Therapeutic responses to ICB vary significantly due to tumor-intrinsic and extrinsic factors.
• The impact of tissue injury on ICB efficacy remains largely unexplored.

Purpose of the Study:

• To investigate the effect of distal traumatic muscle injury on tumor progression and ICB response in murine models.
• To elucidate the immunological mechanisms underlying injury-induced effects on cancer.
• To evaluate the potential of regenerative biomaterials in mitigating adverse effects of injury on cancer outcomes and ICB response.

Main Methods:

• Murine models of distal traumatic muscle injury and multiple tumors were utilized.
• Flow cytometry and immunohistochemistry assessed intra-tumoral CD8+ T cell populations and phenotypes.
• Communication pathways via draining lymph nodes were investigated.
• Biological scaffolds were employed to enhance injury repair.
• Retrospective analysis of breast cancer patients receiving ICB and biological scaffold implantation post-mastectomy was conducted.

Main Results:

• Distal traumatic muscle injury accelerated tumor progression and impaired adjuvant ICB response in mice.
• Injury led to decreased intra-tumoral CD8+ T cell density and effector function, mediated by lymph node communication.
• Enhancing injury repair with a biological scaffold reversed accelerated tumor growth and improved ICB response, dependent on interleukin-4.
• In breast cancer patients, scaffold implantation post-mastectomy correlated with improved overall survival during ICB treatment.

Conclusions:

• Distal traumatic injury can induce immune dysfunction, promoting cancer progression and ICB resistance.
• Interleukin-4-mediated enhancement of wound healing via pro-regenerative biomaterials can counteract injury-induced immunosuppression.
• Regenerative biomaterials represent a promising strategy to improve cancer outcomes, especially in patients undergoing adjuvant or neoadjuvant ICB.
• Targeting wound healing processes may be crucial for optimizing cancer immunotherapy efficacy.