P03.25 Neutralizing extracellular CHP-1 impairs tumor growth and metastasis formation
Journal for ImmunoTherapy of Cancer(2020)
摘要
Background Found in the extracellular compartment, Heat Shock Proteins (HSPs) are actively secreted proteins that modulate the tumor behavior. Extracellular HSPs play a unique role as extracellular chaperones and receptors-binding molecules, favoring the establishment and maintenance of different cancer hallmarks, including immune modulation and evasion. CHP-1, is a ubiquitously expressed protein with chaperone activity and its high expression correlates with high tumor grade and lymph node positivity in different breast and lung cancer subtypes. In addition, CHP-1 is actively and uncanonically secreted by cancer cells in the tumor microenvironment (TME). Materials and Methods Sera cancer patients were analyzed for the presence of CHP-1. To assess the role of extracellular CHP-1 (eCHP-1) in the TME, in vitro experiments on different cell populations have been performed. To dissect the molecular mechanisms, through which eCHP-1 induces cancer progression, have been analyzed specific signaling pathways in cancer and immune cells. Immune cell composition in presence of eCHP-1 in tumors has been identified using flow-cytometry. The characterization of eCHP-1 inhibition as therapeutic approach has been conducted in breast and colon cancer pre-clinical models. Results eCHP-1 activates an autocrine signaling through TLR2, TLR4 and LRP1, promoting tumor progression and metastasis formation in different pre-clinical models. Moreover, eCHP-1 can modulate the immune composition of the TME, making interesting the analysis of its inhibition in cancer immunotherapy. Conclusions eCHP-1 represents a easy accessible protein for diagnosis and targeting in very aggressive canncers. Disclosure Information L. Secli: None. F. Fusella: None. M. Brancaccio: None.
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