Year: 2018
Type: conference-abstract
Abstract: High grade gliomas such as glioblastomas (GBMs) remain virtually incurable diseases. Recent success with immunotherapies for other solid tumors has demonstrated the power of harnessing one’s own immune system to combat malignant cancers. However, on-going clinical trials using checkpoint inhibitors and other approaches show disappointing results in glioma patients. A major known hurdle for many immune therapies is the highly immune-suppressive glioma microenvironment. There are large numbers of myeloid derived suppressive cells (MDSCs) and tumor associated macrophages (TAMs) that promote glioma growth directly and indirectly by block recruitment and infiltration of anti-tumorigenic immune cells (such as T cells). Another potential challenge is the heterogeneity of glioma:immune interactions that generate nuanced but functionally significant differences in different regions of the same patient tumor. To better understand the microenvironmental heterogeneity and glioma:immune cell interactions in different microenvironments, we analyzed cell:cell communication among GSCs, non-stem glioma cells, MDSCs and TAMs in human GBM tissues at the single cell level. We sampled multiple regions from individual GBM tumors during surgical resection to address spatial heterogeneity in immune infiltration and glioma cell genotypes and phenotypes. We performed single cell RNA-sequencing (scRNA-seq) and exome-sequencing as well as immune phenotyping by flow analyses from each fragment separately. Then, using a novel systems biology tool we recently developed, Cell-to-cell Communication Explorer (C2CCE), we systematically analyzed cell-to-cell communication among glioma cells and immune cells at the single cell level. We observed striking spatial heterogeneity of immune infiltration in some patients. We also observed specific cell:cell communication hierarchy among glioma cells, TAMs, and MDSCs. We are currently working on identifying different communication channels between glioma stem cells and non-stem cells with different immune cell types.
Source: Neuro-Oncology
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2900107377