Abstract
BackgroundAlthough melanoma brain metastases (MBM) tend to respond to systemic therapy concordantly with extracranial metastases, little is known about differences in immune cell and vascular content between the brain and other metastatic sites. Here we studied infiltrating immune cell subsets and microvessel density (MVD) in paired intracerebral and extracerebral melanoma metastases.MethodsPaired intracerebral and extracerebral tumor tissue was obtained from 37 patients with metastatic melanoma who underwent craniotomy between 1997 and 2014. A tissue microarray was constructed to quantify subsets of tumor-infiltrating T-cell, B-cell, and macrophage content, PD-L1 expression, and MVD using quantitative immunofluorescence.ResultsMBM had lower CD3+ (p = 0.01) and CD4+ (p = 0.003) T-cell content, lower MVD (p = 0.006), and a trend for lower CD8+ (p = 0.17) T-cell content compared to matched extracerebral metastases. There were no significant differences in CD20+ B-cell or CD68+ macrophage content, or tumor or stroma PD-L1 expression. Low MVD (p = 0.008) and high CD68+ macrophage density (p = 0.04) in intracerebral metastases were associated with improved 1-year survival from time of first MBM diagnosis.ConclusionsAlthough responses to immune-modulating drugs in the body and the brain tend to be concordant, differences were found in MVD and T-cell content between these sites. Studies of these markers should be incorporated into prospective therapeutic clinical trials to determine their prognostic and predictive value.
Highlights
Melanoma brain metastases (MBM) tend to respond to systemic therapy concordantly with extracranial metastases, little is known about differences in immune cell and vascular content between the brain and other metastatic sites
The 5-year survival rate for patients with metastatic melanoma was historically less than 20% [1], clinical outcomes have improved since the approval of targeted therapies and immune checkpoint inhibitors (ICI) which form the foundation of treatment [2,3,4,5]
Three cores taken from representative regions of each tumor were used on the tissue microarray (TMA) to determine site-specific differences in inflammation between intracerebral and extracerebral melanoma metastases
Summary
Melanoma brain metastases (MBM) tend to respond to systemic therapy concordantly with extracranial metastases, little is known about differences in immune cell and vascular content between the brain and other metastatic sites. Conclusions responses to immune-modulating drugs in the body and the brain tend to be concordant, differences were found in MVD and T-cell content between these sites Studies of these markers should be incorporated into prospective therapeutic clinical trials to determine their prognostic and predictive value. While local therapy is effective in the control of MBM, it does not impact extracranial disease or other areas of the brain and can be associated with neurologic complications including radionecrosis Both pembrolizumab [8] and combination ipilimumab and nivolumab have clinical activity against asymptomatic, untreated MBM and have emerged as promising systemic therapy approaches for a select group of MBM patients [9,10,11]
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