Galectin-3 Cooperates with CD47 to Suppress Phagocytosis and T cell Immunity in Gastric Cancer Peritoneal Metastases
Cancer Res. 2023 Sep 22. doi: 10.1158/0008-5472.CAN-23-0783. Online ahead of print.ABSTRACTThe peritoneal cavity is a common site of gastric adenocarcinoma (GAC) metastasis. Peritoneal carcinomatosis (PC) is resistant to current therapies and confer poor prognosis, highlighting the need to identify new therapeutic targets. CD47 conveys a "don't eat me" signal to myeloid cells upon binding its receptor SIRPĪ±, which helps tumor cells circumvent macrophage phagocytosis and evade innate immune responses. Previous studies demonstrated that the blockade of CD47 alone results in limited clinical benefits, suggesting that other target(s) might need to be inhibited simultaneously with CD47 to elicit a strong anti-tumor response. Here, we found that CD47 was highly expressed on malignant PC cells, and elevated CD47 was associated with poor prognosis. Galectin-3 (Gal-3) expression correlated with CD47 expression, and co-expression of Gal-3 and CD47 was significantly associated with diffuse type, poor differentiation, and tumor relapse. Depletion of Gal-3 reduced expression of CD47 through inhibition of c-Myc binding to the CD47 promoter. Furthermore, injection of Gal-3 deficient tumor cells into either wild-type and Lgals3-/- mice led to a reduction in M2 macrophages and increased T cell responses compared to Gal-3 wild-type tumor cells, indicating that tumor cell-derived Gal-3 plays a more important role in GAC progression and phagocytosis than host-derived Gal-3. Dual blockade of Gal...
Source: Cell Research - Category: Cytology Authors: Yibo Fan Shumei Song Yuan Li Shilpa S Dhar Jiankang Jin Katsuhiro Yoshimura Xiaodan Yao Ruiping Wang Ailing W Scott Melissa Pool Pizzi JingJing Wu Lang Ma George A Calin Samir Hanash Linghua Wang Michael Curran Jaffer A Ajani Source Type: research
More News: Adenocarcinoma | Cancer | Cancer & Oncology | Carcinoma | Cytology | Gastric (Stomach) Cancer | Gastroenterology | Peritoneal Cancer | Study