A biologic scaffold-associated type 2 immune microenvironment inhibits tumor formation and synergizes with checkpoint immunotherapy

Sci Transl Med. 2019 Jan 30;11(477):eaat7973. doi: 10.1126/scitranslmed.aat7973.


Biomaterials in regenerative medicine are designed to mimic and modulate tissue environments to promote repair. Biologic scaffolds (derived from decellularized tissue extracellular matrix) promote a wound-healing (proregenerative) immune phenotype and are used clinically to treat tissue loss, including in the context of tumor resection. It is unknown whether a biomaterial microenvironment that encourages tissue formation may also promote tumor development. We implanted a urinary bladder matrix (UBM) scaffold, which is used clinically for wound management, with syngeneic cancer cell lines in mice to study how wound-healing immune responses affect tumor formation and sensitivity to immune checkpoint blockade. The UBM scaffold created an immune microenvironment that inhibited B16-F10 melanoma tumor formation in a CD4+ T cell-dependent and macrophage-dependent manner. In-depth immune characterization revealed an activated type 2-like immune response that was distinct from the classical tumor microenvironment, including activated type 2 T helper T cells, a unique macrophage phenotype, eosinophil infiltration, angiogenic factors, and complement. Tumor growth inhibition by PD-1 and PD-L1 checkpoint blockade was potentiated in the UBM scaffold immune microenvironment. Engineering the local tumor microenvironment to promote a type 2 wound-healing immune signature may serve as a therapeutic target to improve immunotherapy efficacy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biocompatible Materials / pharmacology*
  • Carcinogenesis / immunology*
  • Carcinogenesis / pathology*
  • Cell Line, Tumor
  • Cell Polarity / drug effects
  • Cell Proliferation / drug effects
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Immunotherapy*
  • Inflammation / pathology
  • Interleukin-4 / metabolism
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Macrophages / drug effects
  • Macrophages / pathology
  • Melanoma, Experimental / pathology
  • Mice
  • Myeloid Cells / drug effects
  • Myeloid Cells / metabolism
  • Phenotype
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Tissue Scaffolds / chemistry*
  • Tumor Microenvironment / immunology*
  • Urinary Bladder / physiology
  • Urinary Bladder / ultrastructure
  • Wound Healing / drug effects


  • Biocompatible Materials
  • Interleukin-4