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. Seclì: None. F. Fusella: None. M. Brancaccio: None.