Host's immune response to primary tumours and concomitant brain metastases in the central nervous system

Brain metastases from solid tumours are the most common intracranial neoplasms and significantly impact patients' quality of life and overall survival (OS). Despite advances in oncological therapies, these patients have often been excluded from clinical trials, limiting our understanding of the efficacy of new treatments, such as immunotherapy, in this population. Investigating the tumour microenvironment (TME) of brain metastases is challenging, particularly in determining whether immunotherapy is effective for these lesions. The aim of this study is to investigate the host's immune response to primary tumours and concomitant brain metastases in the central nervous system from various malignancies.

A retrospective study was conducted to examine tumour-infiltrating lymphocytes (TIL) and the expression of programmed cell death 1 and programmed death ligand 1 (PD-L1) in tissue samples from 72 patients with predominant solid tumours and synchronous or metachronous brain metastases. Correlations with different parameters were analysed to evaluate the prognosis of these patients.

All metastatic tumour samples exhibited decreased intraepithelial CD3 and CD8 levels compared to primary tumours, with variable FOXP3 levels and no consistent difference in PD-L1 levels in tumour cells. Programmed death ligand 1 expression in immune cells was generally lower in metastatic lesions compared to primary tumours. The median OS from diagnosis (OS1) was 19.1 months (95% CI: 13.6-35.1), and the median OS from the diagnosis of brain metastases (OS2) was 11.35 months.

The brain TME demonstrates varying levels of TIL and immune checkpoint expression, highlighting the need for further research to develop effective therapies for intracranial metastases.