Anti‐Chi3L1 antibody suppresses lung tumor growth and metastasis through inhibition of M2 polarization

Chitinase 3‐like 1 (Chi3L1) is associated with various biological processes, such as inflammation, tissue repair, proliferation, cell survival, invasion, and extracellular matrix remodeling. Recent studies indicated that Chi3L1 is critical for cancer development and metastasis. In this study, we demonstrate that Chi3L1 serum and tissue levels were significantly increased in lung cancer patients compared with controls. We previously developed an anti‐Chi3L1‐humanized antibody, and here, we investigate its antitumor and antimetastatic effect. The anti‐Chi3L1 antibody attenuated tumor growth and metastasis both in vitro and in vivo in a lung cancer mouse model. These inhibitory effects are associated with signal transducer and activator of transcription 6 (STAT6)‐dependent M2 polarization inhibition. Proteomics analysis revealed that plasminogen (PLG) interacts with Chi3L1 and affects M2 polarization. Chi3L1 plays a critical role in lung cancer progression, and the anti‐Chi3L1 antibody could be a new anticancer therapy. High Chi3L1 expression was correlated with poor overall survival in patients with lung cancer (LC). Here, we show that humanized anti‐Chi3L1 antibody attenuated tumor growth and metastasis in vivo via STAT6‐dependent PLG signaling and M2 polarization inhibition. Proteomics analysis revealed that plasminogen interacted with Chi3L1 and affected M2 polarization. Hence, inhibition of Chi3L1 could be considered as a novel therapeutic strategy for patients with LC.