Research ArticleBIOMATERIALS

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

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Science Translational Medicine  30 Jan 2019:
Vol. 11, Issue 477, eaat7973
DOI: 10.1126/scitranslmed.aat7973

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Biologic scaffolds: Boon or burden for cancer?

Decellularized tissues can serve as scaffolds that promote tissue repair and wound healing—but how do these biologic scaffolds affect tumor formation? Wolf et al. tested the impact of urinary bladder matrix (UBM) on cancer cell growth in mouse models. When implanted with cancer cells, the authors found that UBM altered immune cell recruitment and immune cell phenotypes distinct from tumor-associated immune cell phenotypes. UBM-associated macrophages and T cells were important for inhibiting tumor growth, and UBM improved the efficacy of immune checkpoint inhibition. This study suggests that the prohealing microenvironment induced by UBM could augment anticancer therapies.

Abstract

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.

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