Current treatments, including immunotherapies, are unfortunately not very effective for brain tumors. Only limited tissue samples are available in the context of brain cancers, which hinders research on how to improve therapeutic efficacy for our patients. By maximising the amount of data retrieved from these samples, a new powerful pipeline could bring vital improved insight into the interplay between the diverse cell populations within the tumor immune microenvironment.
Brain cancers, including high-grade gliomas and brain metastasis (BrM), are among the most lethal tumor types and unfortunately there has been only modest progress in improving treatment efficacy in the last decades. While many key advances have been made in the treatment of several cancers with the emergence of different immune checkpoint inhibitors, these therapies have shown clinical benefit in just a small subset of BrMs and little to no efficacy in gliomas.
In order to devise novel strategies to treat brain cancers, including by the enhancement of immune checkpoint inhibition, there is an urgent need to improve our understanding of the interplay between the diverse cell populations within the tumor immune microenvironment (TIME) of these malignancies.
To facilitate this goal, we need to use the often very limited tissue that is obtained from surgical resection of brain cancers as efficiently as possible. Research conducted in the Joyce Lab set out to build a comprehensive multimodular pipeline, enabling in-depth TIME profiling of freshly resected tissue from gliomas and BrM patients, as well as human non-tumor brain tissue. This powerful pipeline maximizes the amount of data retrieved from each precious fresh tissue sample, enabling fluorescence-activated cell sorting of a range of different immune cells for bulk or single cell RNA sequencing, as well as phenotypic characterisation of the TIME. Additionally, different TIME populations can be isolated for ex vivo functional assays.
These analyses can be further complemented by spatial interrogation, proteomic and genomic analyses on frozen tissue. Moreover, the combination of these different methods on partitioned samples, allows for the optimal internal validation of research findings and will be of critical importance for the future development of novel therapeutic strategies in gliomas and BrMs.
This research, published in Nature Protocols*, was conducted in collaboration with Services of Neurosurgery and Pathology of the Lausanne University Hospital. It was supported in part by the Carigest Foundation, ISREC Foundation, the Swiss Bridge Award, Breast Cancer Research Foundation, Ludwig Institute for Cancer Research, and the University of Lausanne. Individual fellowships to lab members were provided by the Austrian Science Fund (FWF), the German Research Foundation (DFG), Fondation Medic and EMBO.
*An integrated pipeline for comprehensive analysis of immune cells in human brain tumor clinical samples