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

Anna Ruta, Elise F Gray-Gaillard, Jordan A Garcia

    Biorxiv : the Preprint Server for Biology
    |February 12, 2026
    PubMed

    Insights

    Traumatic muscle injury accelerates tumor growth and worsens immunotherapy response by impairing T cells. Enhancing wound healing with biomaterials improved outcomes and survival in patients receiving immune checkpoint blockade (ICB).

    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.

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