Blocking the FSTL1-DIP2A Axis Improves Anti-tumor Immunity

Publication date: 14 August 2018Source: Cell Reports, Volume 24, Issue 7Author(s): Chie Kudo-Saito, Akiko Ishida, Yuji Shouya, Koji Teramoto, Tomoyuki Igarashi, Ryoko Kon, Kenji Saito, Chihiro Awada, Yamato Ogiwara, Masayoshi ToyouraSummaryImmune dysfunction is a strong factor in the resistance of cancer to treatment. Blocking immune checkpoint pathways is a promising approach to improve anti-tumor immunity, but the clinical efficacies are still limited. We previously identified follistatin-like 1 (FSTL1) as a determinant of immune dysfunction mediated by mesenchymal stromal/stem cells (MSCs) and immunoregulatory cells. Here, we demonstrate that blocking FSTL1 but not immune checkpoint pathways significantly suppresses cancer progression and metastasis in several mouse tumor models with increased MSCs. Expression of DIP2A (the receptor of FSTL1) in tumor cells is critical for FSTL1-induced immunoresistance. FSTL1/DIP2A co-positivity in tumor tissues correlates with poor prognosis in NSCLC patients. Thus, breaking the FSTL1-DIP2A axis may be a useful strategy for successfully inducing anti-tumor immunity.Graphical Abstract
Source: Cell Reports - Category: Cytology Source Type: research