Tmic-49. Abrogating Cd70 Expression in Gbm Results in a Reduced Immunosuppressive Tumor Microenvironment
Year: 2019
Type: conference-abstract
Abstract: BACKGROUND We found that CD70, as an immune modulator, in GBM plays a critical role in immunosuppression and tumor progression. Although CD70+ tumors recruit more CD3+ T cells than CD70— tumors do in patients with GBM, CD70 on GBM is also found to be involved in promoting CD8+ T cell death. The experiments by overexpressing or silencing CD70 in a primary tumor demonstrate that it can alter cell growth, survival, migration, and morphology of GBM cells. CD70 is negatively correlated with survival in patients with gliomas. These results suggest that CD70 is involved in immunosuppression in GBM. OBJECTIVE To determine if abrogating CD70 in tumor using CD70CAR-T cells could reverse the immunosuppressive microenvironment and enhance overall endogenous tumor immunity against both CD70+ and CD70— tumors, which might help to overcome a key obstacle— tumor-heterogeneity using single-targeted CAR-T cell therapy. METHODS CD70 was overexpressed (~75% positivity) in KR158 GBM line. Murine CD70CAR T cells were used to eliminate CD70+ tumors in an immunocompetent orthotopic tumor mouse model. Tumor-bearing mice were administered the CD70CAR T and vector-tranduced T cells, followed by IVIS imaging for tumor growth. The presentation and phenotype of CAR T cells and endogenous immune cell populations in tumors and spleens were measured. RESULTS Five weeks post treatment, CD4+ T cells were found to be the dominant T cell population in tumors for both CAR-T and endogenous T cells. While the CAR-T cells shrank the tumors, fewer PD-1 expressing endogenous T cells, as well as granulocytic MDSC, but not monocytic MDSC were observed in the tumor (not in spleen) for the CAR-T group, compared to the vector group. No significant changes were seen for NK cells and Tregs between the groups. CONCLUSION This study suggests that eliminating CD70+ tumor cells may reverse the immunosuppressive landscape of the tumor microenvironment.
Source: Neuro-Oncology
Institutions: University of Florida, Harbin Medical University
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2984219985