Elucidating the Leptomeningeal Immune Response to Cancer With Single-Cell Proteogenomic Profiling

Speaker: Jan Remsik, PharmD, PhD

Postdoctoral Fellow, Adrienne Boire Lab
Memorial Sloan Kettering Cancer Center

Metastases to the central nervous system from solid primary tumors are a frequent and fatal complication of cancer with limited therapeutic options. Despite the advent of immunotherapy, it remains largely unknown whether and how metastatic cells in the brain and surrounding cerebrospinal fluid (CSF)-filled leptomeninges interact with the immune system.

To approach these interactions in an unbiased manner, Jan Remsik and his colleagues profiled an unexpectedly heterogeneous population of cell types in human and mouse CSF with single-cell analytics. These samples were inherently challenging to process due to a relatively low number of cells from each human subject or mouse collection, extreme cell fragility, and contamination by myelin and other unwanted debris in the case of the mouse samples. Since FACS-sorted samples suffered an unbearable amount of stress that prevented their processing, the team used the LeviCell 1.0 system to deplete the debris and enrich for viable cells in stress-free conditions. Incorporating the LeviCell run into their pipeline resulted in the capture of sufficient numbers of high-quality cells for CITE-seq. Such a proteogenomic approach, combining more than 100 cell surface signals with whole transcriptome sequencing, allowed Remsik and his colleagues to elucidate the response of the CSF immune system to cancer at an unprecedented resolution.

About Dr. Jan Remsik:

Jan Remsik is a Postdoctoral Fellow at the Adrienne Boire Lab at Memorial Sloan Kettering Cancer Center. Intrigued by the ability of cancer cells to colonize the immune-populated cerebrospinal fluid, Jan Remsik generated a series of syngeneic animal models of leptomeningeal metastasis (LM) and accompanying single-cell atlases of human and mouse LM. Using these tools, he studies the mechanistic nature of cancer-immune cell interactions to develop alternative immune-therapeutic approaches against metastasis within this space.