Abstract
Diverse subsets of antigen-presenting cells (APCs) reside within solid tumors and have the potential to capture and present cancer antigens locally. The cellular and molecular interactions, as well as the challenges and outcomes of intratumoral cancer antigen presentation are poorly understood. Our laboratory has recently pioneered studies demonstrating that fibroblasts present cancer antigens to CD4 T cells within lung tumors. We proposed a model wherein intratumoral APCs sustain CD4 T cells independently of lymph nodes, known as the "Second Touch Hypothesis." Currently, we are exploring the landscape of lung cancer APCs and seeking to understand how the tumor microenvironment affects them. During the first of my talk, I will showcase space-aware transcriptomic maps of mesenchymal APCs in human lung tumors. I will pinpoint two subsets of antigen-presenting mesenchymal cells with different organization patterns in tumor ecosystems: an alveolar epithelial-derived and a myeloid cell derived. In the second part, I will reveal a double-edged sword function for type I interferons. Specifically, I will explain how interferon-inducible GBP-2 induces pyroptotic death in intratumoral dendritic cells. By elucidating the complexities of cancer antigen-presenting cells, my laboratory aims to pave new pathways in more effective cancer immunotherapies.

Biosketch
Dr. Maria Tsoumakidou, MD, PhD is a board-certified respiratory specialist and Associate Professor of Physiology at the National and Kapodistrian University of Athens. A leading expert in cancer immunology, her research focuses on antigen-presenting cells, tumor escape mechanisms, and ex vivo models for biomarker discovery and drug screening.
She has published over 30 high-impact papers (>4,000 citations, h-index 27) and has received multiple prestigious awards, including the Clinical and Research Excellence Award from the Hellenic Thoracic Society. In 2023, she was awarded an ERC Consolidator Grant to develop innovative cancer immunotherapies by leveraging antigen-presenting fibroblasts. Her work challenges conventional paradigms of immunosuppression and introduces groundbreaking strategies to enhance T cell-mediated immunity in cancer treatment.