A new study into brain metastasis has identified an immune target with translational potential. 

The study, conducted by researchers at the Spanish National Cancer Research Centre (CNIO), has identified macrophage migration inhibitory factor (MIF)–mediated reprogramming of CD74‑positive microglia and macrophages as a central vulnerability in brain metastasis. 

The work, led by Manuel Valiente and scientists at CNIO, shows that tumour‑derived MIF alters the functional state of microglia and infiltrating macrophages in the brain, converting them from a potentially protective role into a pro‑metastatic one.  

In multiple experimental models and fresh patient‑derived brain metastasis samples, inhibition of the MIF–CD74 signalling axis significantly reduced metastatic progression. 

The investigators also identified secreted MIF as a candidate liquid biopsy biomarker detectable in cerebrospinal fluid, supporting a translational, biomarker‑guided clinical strategy. 

“Brain metastases develop in up to 30% of patients with advanced solid tumours, most commonly arising from lung cancer, breast cancer, melanoma, and colorectal cancer, and remain an area of substantial unmet medical need,” Valiente said. 

“Despite recent advances in systemic therapies, patients with brain metastases have historically been excluded from many clinical trials, limiting progress in the development of targeted treatments.  

“By focusing on brain‑specific immune–microenvironment interactions rather than tumour‑intrinsic alterations alone, the CNIO findings open a new therapeutic avenue that may be applicable across multiple primary tumour types.” 

“The publication of this work in Cancer Research provides strong mechanistic and translational rationale to pursue biomarker‑driven clinical strategies,” added Dr Kazuko Matsuda, Chief Medical Officer at biopharmaceutical company MediciNova. 

“We hold granted patents covering MN‑166 for preventing and minimising cancer metastasis across multiple solid tumour types, including pancreatic, lung, breast, colorectal and ovarian cancers, as well as melanoma.  

“Our focus is now on advancing future clinical investigations and responsibly translating these insights into studies designed for patients with brain metastases.”