Melanoma brain metastases have lower T-cell content and microvessel density compared to matched extracranial metastases
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LABORATORY INVESTIGATION
Melanoma brain metastases have lower T‑cell content and microvessel density compared to matched extracranial metastases Sarah A. Weiss1 · Christopher Zito1,2 · Thuy Tran1 · Kazuki Heishima1,5 · Veronique Neumeister3,6 · John McGuire3,6 · Adebowale Adeniran3 · Harriet Kluger1 · Lucia B. Jilaveanu1,4 Received: 26 May 2020 / Accepted: 10 September 2020 © The Author(s) 2020
Abstract Background Although 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. Methods Paired 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. Results MBM 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. Conclusions Although 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. Keywords Melanoma · Metastases · Brain · PD-L1 · Immune markers · Microvessel density
* Lucia B. Jilaveanu [email protected] Sarah A. Weiss [email protected] 1
Department of Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT, USA
2
Department of Biology, School of Health and Natural Sciences, University of Saint Joseph, West Hartford, CT, USA
3
Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
4
Section of Medical Oncology, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06520, USA
5
Present Address: Gifu University, Gifu, Japan
6
Present Address: Akoya Biosciences, Marlborough, MA, USA
Abbreviations CNS Central nervous system FDA Food and Drug Administration ICI Immune checkpoint inhibitors IRB Institutional Review Board MBM Melanoma brain metastases MVD Microvessel density PD-L1 Programmed death ligand 1 QIF Quantitative immunofluorescence SRS Stereotactic radiosurgery TIL Tumor infiltrating lymphocytes TMA Tissue microarray WBRT Whole brain radiation
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