Tissue Injury and Biomaterial Treatment Modulate Tumor Growth and Response to Immunotherapy
Immunotherapies have transformed cancer care; however, tumor intrinsic and extrinsic factors contribute to high variability in therapeutic responses. While tissue injuries can impact cancer recurrence and metastatic spread, little is known about their potential to effect immune checkpoint blockade (ICB) response. In this study, we reveal that distal traumatic muscle injury accelerated progression and impaired adjuvant ICB response of multiple murine tumors. This injury-induced accelerated tumor growth coincided with decreased intra-tumoral density and effector phenotype of tumor-reactive CD8 <sup>+</sup> T cells and relied on communication through a shared draining lymph node. Enhancing injury repair using a biological scaffold abrogated the injury-induced accelerated tumor growth in an interleukin-4-dependent manner and improved ICB response. In a retrospective cohort analysis of breast cancer patients undergoing ICB treatment, biological scaffold implantation following mastectomy was associated with increased overall survival. This work suggests that injury-driven immune dysfunction may contribute to cancer progression and ICB resistance, but enhancing wound healing with pro-regenerative biomaterials may offer a viable strategy for mitigating adverse cancer outcomes, particularly in the setting of adjuvant and neoadjuvant ICB.
Authors
- DM Pardoll
- C. Cherry
- David R. Maestas (ORCID: https://orcid.org/0000-0002-8207-1835)
- Jordan Garcia (ORCID: https://orcid.org/0000-0002-3336-0294)
- Anna Ruta (ORCID: https://orcid.org/0000-0002-4258-1785)
- Joscelyn C. Mejías (ORCID: https://orcid.org/0000-0003-4397-9741)
- Kavita Krishnan (ORCID: https://orcid.org/0000-0003-1345-0249)
- Matthew T. Wolf (ORCID: https://orcid.org/0000-0002-0328-2475)
- Michael Patatanian
- Kellie N. Smith (ORCID: https://orcid.org/0000-0002-6295-8930)
- Peter Abraham (ORCID: https://orcid.org/0009-0008-9506-8193)
- Yusef Mathkour
- Locke Davenport Huyer
- Elise Gray-Gaillard
- Jennifer H. Elisseeff
Institutions
- Dalhousie University (CA)
- Johns Hopkins University (US)
- University of Pittsburgh (US)
- Johns Hopkins Medicine (US)
- The Wallace H. Coulter Department of Biomedical Engineering (US)
- Frederick National Laboratory for Cancer Research (US)
- National Cancer Institute (US)
- Sidney Kimmel Comprehensive Cancer Center (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-02-04
- DOI
- https://doi.org/10.64898/2026.02.02.703323
- Primary Topic
- Cancer, Stress, Anesthesia, and Immune Response
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- U.S. Department of Health and Human Services
- Johns Hopkins University
- Integra LifeSciences
- National Institutes of Health
- National Cancer Institute
- Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University