Figure 11.

Schematic model of Rab37-mediated exocytosis of CHI3L1 protumor protein in T cells or macrophages to foster an immunosuppressive tumor microenvironment that is blocked by CHI3L1 neutralizing antibodies through activating anti-tumor immune response and reducing cancer oncogenic signals. This study provides cell, animal and clinical evidence that exocytosis of chitinase 3-like-1 (CHI3L1) protumor protein mediated by Rab37 vesicles in T cells and macrophages drives tumor progression and immunosuppressive microenvironment (Left). These immunosuppressive tumor microenvironment and aggressive tumor phenotype are blocked by CHI3L1 neutralizing antibodies through shifting M2 to anti-tumor M1 macrophages, decreasing regulatory T cells/cytotoxic T cells ratio and attenuating oncogenic cancer signaling to reduce tumor growth and metastases (Right).