Year: 2025
Type: article
Abstract: Tumor controls its immunity by educating its microenvironment, including regulating polarity of tumor associated macrophages. It is well documented that cancer cells release PKM2 to facilitate tumor progression. We report here that the extracellular PKM2 (EcPKM2) modulates tumor immunity by facilitating M2 macrophage polarization in tumors. EcPKM2 interacts with integrin α v β 3 on macrophage to activate integrin-FAK-PI3K signal axis. Activation of FAK-PI3K by EcPKM2 suppresses PTEN expression, which subsequently upregulates arginase1 (Arg1) expression and activity in macrophage to facilitate M2 polarity. Our studies uncover a novel and important mechanism for modulation of tumor immunity. More importantly, an antibody against PKM2 that disrupts the interaction between EcPKM2 and integrin α v β 3 is effective in converting M2 macrophages to M1 macrophages in tumors, suggesting a new therapeutic strategy and target for cancer therapies. Combination of the anti-PKM2 antibody with checkpoint blockades provides enhanced treatment effects.
Source: Cancer Immunology Immunotherapy
Institution: Georgia State University
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,590
OpenAlex ID: W4410217772