Lance Liotta,
Co Director,
George Mason University
Dr. Liotta received his MD and PhD (Bioengineering) from Case Western Reserve. He is currently Co-Director and Co-Founder of the Center for Applied Proteomics and Molecular Medicine at George Mason University. Prior to this appointment, Dr. Liotta served as Chief of the Laboratory of Pathology, NCI, and Deputy Director of NIH. Dr. Liotta has invented and patented technologies in the fields of molecular diagnostics, cancer molecular therapeutics, microdissection (Laser Capture Microdissection), and proteomics (Reverse Phase Protein Microarrays, Biomarker harvesting nanoparticles, preservation chemistries for molecular analysis, and Protein Painting for protein binding site hotspot mapping), that have been used to make broad discoveries in disease biology, cancer diagnostics, and drug discovery. He is Board Certified in Anatomic Pathology and Medical Director of the GMU CAP/CLIA certified clinical proteomics Lab. >670 publications, >100 patents, ISI highly cited investigator.
Reversing EV Induced Tumor Immune Suppression at the Sentinel Lymph Node: Role of Secretory Autophagy/Mitophagy
Wednesday, 15 December 2021 at 14:30
Add to Calendar ▼2021-12-15 14:30:002021-12-15 15:30:00Europe/LondonReversing EV Induced Tumor Immune Suppression at the Sentinel Lymph Node: Role of Secretory Autophagy/MitophagyExtracellular Vesicles (EVs): Technologies and Biological Investigations in Coronado Island, CaliforniaCoronado Island, CaliforniaSELECTBIOenquiries@selectbiosciences.com
The goal is to reverse cancer immune evasion at the level of the sentinel lymph node. Reduced expansion of CD8+Tcells and other innate immune effector cells in the cancer draining SLN is associated with progression and resistance to checkpoint inhibitors. Cancer derived extracellular vesicles (EVs) that are PD-L1 positive suppress immune recognition at the level of the SNL. Experimental goal: To remodel the SNL to overcome cancer EV-associated immune suppression and induce immune rejection of the tumor. We developed three methodologies for this project a) Collection of draining lymph fluid to characterize extracellular vesicles (EVs) shed by 4T1 syngeneic breast tumors growing in the mammary fat pad. b) Chromatographic separation and characterization of the repertoire of EVs shed by tumors into the tumor microenvironment interstitial space using western blotting, mass spectrometry, and electron microscopy. c) Nanoparticle delivery of purified classes of EVs to the tumor draining SNL in combination with cytokine chemoattractants for innate immune cells. Results: Murine and human breast cancer cell lines shed classic exosomes and autophagosomes. The latter are shed extracellularly by the activation of the secretory autophagy pathway. The classic exosomes(exosome marker positive) contained PD-L1. In contrast the LC3 I/II P62 positive double membrane extracellular autophagosomes contained mitochondrial components (mitophagy). SLN immune cell populations could be massively remodeled by introducing hydrogel nanoparticles that affinity release chemoattractants locally in the subcapsular sinus. Nanoparticles could also be used to deliver concentrated packages of EVs of different classes to the SLN. Introduction of the large CD81 negative VEGF positive EV population (amphisome characteristics) to the SLN augmented tumor growth, angiogenesis, and metastasis, even when cytokine induction was used to remodel the SLN. In marked contrast, introduction of the PD-L1 positive exosomes to the SLN in combination with nanoparticle release of T-cell and dendritic cell chemoattractants, induced immune rejection of the syngeneic breast cancer, reducing tumor growth and blocking metastasis. The findings demonstrate that different classes of EVs have opposite effects on cancer immune evasion at the level of the SLN and that EV mediated immune suppression can be reversed by SLN remodeling to augment dendritic and CD8 T cells.
Add to Calendar ▼2021-12-13 00:00:002021-12-15 00:00:00Europe/LondonExtracellular Vesicles (EVs): Technologies and Biological InvestigationsExtracellular Vesicles (EVs): Technologies and Biological Investigations in Coronado Island, CaliforniaCoronado Island, CaliforniaSELECTBIOenquiries@selectbiosciences.com
Add to Calendar ▼2021-12-15 14:30:002021-12-15 15:30:00Europe/LondonReversing EV Induced Tumor Immune Suppression at the Sentinel Lymph Node: Role of Secretory Autophagy/MitophagyExtracellular Vesicles (EVs): Technologies and Biological Investigations in Coronado Island, CaliforniaCoronado Island, CaliforniaSELECTBIOenquiries@selectbiosciences.com
