The phenotypic and transcriptomic landscape of tumor associated myeloid cells during primary and relapsing ovarian cancer
Olympia Papantonopoulou1, Kevin Bassler1, Anna Doeser2, Michael Mallmann2, Walther Kuhn2, Peter Mallmann3, Kristian Haendler1, Joachim L. Schultze1,3* Andreas Schlitzer1,3,4*
1 Genomics&Immunoregulation, LIMES Institute, University of Bonn, 53115 Bonn, Germany
2 Department of Gynecology and Obstetrics, University Hospital Bonn, Bonn, Germany
3 Department of Gynecology and Obstetrics, University Hospital Cologne, Cologne, Germany
4 Platform for Single Cell Genomics and Epigenomics at the DZNE and the University of Bonn, Bonn, Germany
5 Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 138648, Singapore
Ovarian cancer (OvCa) is the most lethal gynecological type of cancer. During its pathogenesis, myeloid cells, such as monocytes, dendritic cells (DCs) and neutrophils, infiltrate the tumor microenvironment and such infiltration is correlated with poor patient prognosis and survival. The myeloid compartment presents as a heterogeneous population, with distinct functional, phenotypic and transcriptional profiles. This plasticity and heterogeneity presents a great challenge for the development of targeted immunotherapies in the treatment of OvCa.
Here, we investigate the phenotypic profiles and the role of myeloid cells in the progression of OvCa. We applied single-cell mRNA sequencing to freshly isolated cells from the ascitic fluid of primary diagnosed and relapsing OvCa patients. Multidimensional analysis of single-cell transcriptional networks elucidates the intra-tumoral heterogeneity of monocyte-derived cells and DCs, revealing distinct abundance, phenotypic profiles and transcriptional regulation patterns according to the progression of the disease.
Overall, our single-cell analysis enables for the first time the global deciphering of the myeloid cell network within the tumor microenvironment over the course of OvCa and paves the way for new myeloid cell targeted immunotherapies to modify the tumor microenvironment and to allow for a more efficient anti-tumor immune response.