Leonardo F. Jurado, Andrew W. Daman, Ziyi Li, Vanessa M.S. Ross, Kristina Nikolaou, Kim A. Tran, Oleg Loutochin, Victor A. McPherson, Renaud Prével, Raquel Tarancón, Katalina Couto, Erwan Pernet, Nargis Khan, Jin-Gyu Cheong, Reshma Ramaiah, Mythili Ketavarapu, Eva Kaufmann, Michael S. Glickman, Ajitha Thanabalasuriar, Steven Z. Josefowicz, Maziar Divangahi
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引用次数: 0
Abstract
In patients with non-muscle invasive bladder cancer, the standard immunotherapy involves intravesical Bacillus Calmette-Guérin (BCG). However, its success requires repeated doses, and ∼50% of patients do not benefit. Using a preclinical orthotopic bladder cancer model, we found that a single intravesical dose of combined BCG and β-glucan immunotherapy eradicated aggressive tumors, resulting in 100% survival. Through single-cell transcriptomic/epigenomic analysis, flow cytometry, and intravital imaging, we show that BCG and β-glucan reprogrammed hematopoietic stem and progenitor cells with imprinting in innate immune cells, particularly neutrophils. Reprogrammed neutrophils exhibited increased reactive oxygen species (ROS) production and infiltration into the tumor core, reducing tumor vascularization and growth. The tumor microenvironment can convert neutrophils into protumor cells; BCG and β-glucan prevented this conversion, promoting sustained antitumoral activity. These findings support β-glucan as a safe, effective adjuvant to enhance BCG immunotherapy in bladder cancer and other solid tumors.
期刊介绍:
Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.