Single-Cell Profiling of Human Tumors and Inflamed Tissues Reveals Therapeutically Targetable Tumor-Unique Immune Subsets

The composition of the immune infiltrate in the human tumor microenvironment is a critical determinant of disease progression. Immunotherapies to treat cancer have achieved remarkable successes, but an inherent weakness of current treatment approaches is that the targeted immune subsets are not exclusive to tumors. In an effort to identify tumor-unique immune features that are distinct from general inflammatory processes, we used complementary single-cell analysis approaches to compare the immune landscape in human tumors and site-matched non-malignant, inflamed tissue samples. 

We found that the immune infiltrate in inflamed tissues showed substantial phenotypic congruence with the tumor, but computational analyses identified putative, tumor-unique signaling networks between antigen-presenting cells (APCs) and regulatory T cells (Tregs). Subsequent experimental validation confirmed an intratumoral IL-1 network between APCs and Tregs. Intratumoral Tregs were uniquely identified by ICOS and IL-1R1 cell surface expression, thus allowing for tumor-specific depletion.
 

• Advanced single-cell analysis of human tumor-tissues relative to inflamed human tissues
• Computational and machine learning analyses reveal previously unidentified tumor-unique immune subsets and signaling axes
• Experimental validation confirms a tumor-unique subset of regulatory T cells (Tregs)
• A blueprint for a novel discovery approach of immunotherapeutic targets in the human tumor microenvironment

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Speaker Biography

Florian Mair obtained his MSc from the University of Vienna (Austria) in 2008 and his PhD from the University of Zurich (Switzerland) in 2014. Currently, he is working as an immunologist at the Fred Hutchinson Cancer Research Center in Seattle (USA), where his main interest is dissecting the function of myeloid antigen-presenting cells (APCs) in non-lymphoid tissues during steady state and disease, in particular cancer.

One key aspect of his work is the development of cutting-edge single-cell analysis techniques, including high-parameter flow cytometry and multi-omic scRNA-sequencing. His ultimate goal is to leverage these advanced technologies to understand how to manipulate immune cells for therapeutic use and ultimately improve human health. He is an ISAC Marylou scholar and an AAI Computational Intersect fellow.