Blosser, R. L. | Search bioRxiv

bioRxiv2021

Biomaterials direct functional B cell response in a material specific manner

B cells are an adaptive immune target of biomaterials development in vaccine research but despite their role in wound healing have not been studied in tissue engineering and regenerative medicine. We evaluated the B cell response to biomaterial scaffold materials implanted in a muscle wound; a biological extracellular matrix (ECM) and synthetic polyester polycaprolactone. In the local muscle tissue, small numbers of B cells are recruited in response to tissue injury and biomaterial implantation. ECM materials induced plasmablasts in lymph nodes and antigen presentation in the spleen while the synthetic PCL implants delayed B cell migration and induced an antigen presenting phenotype. In muMt- mice lacking B cells, the fibrotic response to the synthetic biomaterials decreased. Immunofluorescence confirmed antigen presenting B cells in fibrotic tissue surrounding silicone breast implants. In sum, the adaptive B cell immune response to biomaterial depends on composition and induces local, regional and systemic immunological changes.

bioengineering↗

bioRxiv2019

Targeting glutamine metabolism enhances tumor specific immunity by inhibiting the generation of MDSCs and reprogramming tumor associated macrophages

Myeloid cells comprise a major component of the Tumor Microenvironment (TME) promoting tumor growth and immune evasion. By employing a novel small molecule inhibitor of glutamine metabolism not only were we able to inhibit tumor growth but we markedly inhibited the generation and recruitment of Myeloid Derived Suppressor Cells (MDSC). Targeting tumor glutamine metabolism led to a decrease in CSF-3 and hence recruitment of MDSC as well immunogenic cell death leading to an increase in inflammatory Tumor Associated Macrophages (TAMs). Alternatively, inhibiting glutamine metabolism of the MDSC themselves led to activation induced cell death and conversion of MDSC to inflammatory macrophages. Surprisingly, blocking glutamine metabolism also inhibited IDO expression of both the tumor and myeloid derived cells leading to a marked decrease in kynurenine levels. This in turn inhibited the development of metastasis and further enhanced anti-tumor immunity. Indeed, targeting glutamine metabolism rendered checkpoint blockade-resistant tumors susceptible to immunotherapy. Overall, our studies define an intimate interplay between the unique metabolism of tumors and the metabolism of suppressive immune cells.

immunology↗