JCB-JEM Symposium: Miriam Merad - Mapping Myeloid Cell Contribution to Cancer Lesions
13Miriam Merad gives her talk "Mapping Myeloid Cell Contribution to Cancer Lesions" as part of the JCB-JEM symposium on Tackling Cancer Plasticity and Heterogeneity at The Rockefeller University in New York, October 9th, 2018. https://rupress.org/pages/jcb-jem-symposium-tackling-cancer-plasticity-and-heterogeneity
Dr. Merad’s work at Mount Sinai School of Medicine focuses on the tumor myeloid microenvironment. Myeloid antigen-presenting cells play a key role in anti-tumor immunity by acting as sensors of injury, tumor cell growth, cell death, and microbial signals and releasing inflammatory molecules that shape the tumor microenvironment (TME) and the tumor T-cell environment. Macrophages are often the largest immune cell compartment in tumor lesions and play a key role in tissue remodeling and modulation of tumor immunity. Knowledge of human macrophages primarily comes from in vitro studies of monocyte-derived macrophages, defining the M1/M2 paradigm. But this is an incomplete definition that ignores the tissue-resident macrophage lineage, so the Merad lab has used fate-mapping studies to examine and characterize tissue-resident macrophages and their recruitment. Mapping these cells can provide critical information to understand pathophysiological processes and develop targeted therapies.
In this talk, Dr. Merad focuses on early non-small cell lung cancer (NSCLC). Using mass spectrometry analyses of early lung cancer lesions as well as modeling studies in mice, Dr. Merad and colleagues mapped the immune cell compartment and used scRNA sequencing to provide an unbiased analysis of lung tumor-associated immune cells. They identify different temporal and spatial waves of ontogenically distinct adult and embryonic macrophage populations that accumulate in tumor lesions. They show that adult hematopoiesis does not give rise to tumor-resident macrophages, even when recruited to tissues , indicating the importance of understanding the biology of these cells specific to tissue site. Interestingly, embryonic macrophages are the first to interact with tumor cells and promote tumor growth. Upon tumor progression, embryonic macrophages are excluded from the tumor lesion and likely contribute to shielding the tumor lesion from cytotoxic anti-tumor immunity, potentially through the activation of stromal fibroblasts.
Video © Rockefeller University Press