Скачать или смотреть SCOG Virtual Lecture Series - Florian Mair (ETH, Zurich)

‘Disentangling human tumor-unique immune alterations from non-malignant tissue inflammation using multi-omic single cell analysis’

Immunotherapies to treat cancer have achieved remarkable successes, but major challenges persist. An inherent weakness of current treatment approaches is that therapeutically targeted pathways are not only found in tumors, but also in tissue microenvironments, particularly inflamed tissues. This confounding overlap complicates treatment as well as predictions of treatment outcome. In an effort to identify potential tumor-unique immunotherapeutic targets that are distinct from general tissue inflammation, we used complementary single-cell analysis approaches to interrogate immune cell alterations and interactions in human head and neck squamous cell carcinomas (HNSCC) and site matched non-malignant, inflamed oral tissues.
Using a combination of scRNA-sequencing and high-dimensional flow cytometry we found that a distinct population of intratumoral regulatory T cells (Tregs) is receiving T cell receptor (TCR) signals from antigen-presenting cells (APCs). This Treg population can be uniquely identified among all hematopoietic cells in the tumor by co-expression of ICOS and IL-1 receptor type 1 (IL-1R1), allowing therapeutic targeting and depletion by bispecific antibodies or logic-gated CAR T cells. In addition, we used targeted transcriptomics and protein profiling (AbSeq) to assess the functional response of these human intratumoral IL-1R1+ Tregs after stimulation via the T cell receptor or cytokines.
Overall, our work provides a blueprint for identifying tumor-unique therapeutic targets distinct from general inflammatory patterns in other tumors and reveals a possible strategy for specific depletion of intratumoral Tregs.

Biography:
Florian is currently working as Scientific Director of Cytometry and Senior Scientist Immunology at ETH Zurich, Switzerland. After graduating with a PhD in Molecular Life Sciences from the University of Zurich, Switzerland in 2014, he spent several years at the Fred Hutchinson Cancer Research Center in Seattle, USA. During the past decade, he has been involved extensively with different cytometry platforms (conventional, spectral and mass cytometry) as well as scRNA-sequencing techniques, including multi-omic methods. His main scientific interests are the function of dendritic cells and T cells in non-lymphoid tissues during health and disease.

More info:
https://www.singlecell.de; Twitter: @singlecellomics