| Summary: | Summary: Immune 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. : Using mouse metastasis models, Kudo-Saito et al. demonstrate the therapeutic potential of anti-FSTL1 mAbs via a mechanism that is distinct from immune checkpoint pathways. Because FSTL1 expression in tumor tissues correlates with poor prognosis, targeting FSTL1 may be useful for treating lung cancer patients. Keywords: FSTL1, cancer metastasis, immunosuppression, immune exhaustion, mesenchymal stromal/stem cells, immune checkpoint, antibody, aging, lung cancer
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