ArticleCancer immunology research2022
Microenvironmental Landscape of Human Melanoma Brain Metastases in Response to Immune Checkpoint Inhibition.
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Article in Cancer immunology research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38citing papers in PubMed
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Who cites it
38 citing papers in PubMed.
- Integrating tumor and immune cell transcriptomics to predict immune checkpoint inhibitor primary resistance in metastatic melanoma.Oncoimmunology · 2026Article
- Spatially-resolved single-cell imaging of melanoma brain metastases identifies localized immune patterns predictive of immune checkpoint blockade response.Neuro-oncology · 2026Article
- Future directions in the treatment of brain metastases: evaluating the role of cellular players in the tumour microenvironment.Acta neuropathologica · 2026Review
- Single-cell and spatial profiling in cancer biology and clinical oncology.Nature cancer · 2026Review
- Single-cell advances in the investigation of the pathogenesis and treatment of brain metastasis.Neuro-oncology advances · 2026Review
- Unraveling the Enigma of Melanoma Brain Metastasis: New Molecular Insights and Therapeutic Directions.International journal of molecular sciences · 2026Review
- EnhancedScience advances · 2025Article
- CDK12/13 inactivation triggers STING-mediated antitumor immunity in preclinical models.The Journal of clinical investigation · 2025Article
- Biomarkers of immunotherapy response in neuro-oncology.Neuro-oncology advances · 2025Review
- Integrative spatial omics reveals distinct tumor-promoting multicellular niches and immunosuppressive mechanisms in Black American and White American patients with TNBC.Nature communications · 2025Article
- Incorporating hierarchical information into multiple instance learning for patient phenotype prediction with single-cell RNA-sequencing data.Bioinformatics (Oxford, England) · 2025Article
- Microfluidic technologies for enhancing the potency, predictability and affordability of adoptive cell therapies.Nature biomedical engineering · 2025Review
- Cholinergic T cells revitalize the tumor immune microenvironment: TIME to ChAT.Nature immunology · 2025Review
- Integrated analysis of molecular and clinical features associated with overall survival in melanoma patients with brain metastasis.Acta neuropathologica communications · 2025Article
- Progress in personalized immunotherapy for patients with brain metastasis.NPJ precision oncology · 2025Review
- Integrated cancer cell-specific single-cell RNA-seq datasets of immune checkpoint blockade-treated patients.Scientific data · 2025Article
- CTLA-4 and PD-1 combined blockade therapy for malignant melanoma brain metastases: mechanisms, challenges, and prospects.Frontiers in immunology · 2025Review
- Role of Galectin-1 in the Pathogenesis of Melanoma.Journal of cancer science and clinical therapeutics · 2025Article
- Case Report: T-Dxd plus bevacizumab in a patient with brain metastases from rectal cancer with HER2 amplification.Frontiers in oncology · 2025Article
- Effect of neutrophils on tumor immunity and immunotherapy resistance with underlying mechanisms.Cancer communications (London, England) · 2025Review
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Authors and funding
45 authors.
Christopher Alvarez-Breckenridge *Departments of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0001-5997-6532
Samuel C Markson *Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-9053-9867
Jackson H StockingDepartment of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0003-2759-2125
Naema NayyarDepartment of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0003-3436-8404
Matt LastrapesBroad Institute, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts.ORCID 0000-0003-0780-3466
Matthew R StricklandDepartment of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0001-7845-0712
Albert E KimDepartment of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0003-2359-6209
Magali de SauvageDepartment of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0001-9486-945X
Ashish DahalDepartment of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0002-0413-7288
Juliana M LarsonDepartment of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0001-6897-5355
Joana L MoraBroad Institute, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts.ORCID 0000-0002-5913-1107
Andrew W NaviaDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts.ORCID 0000-0002-5429-8012
Robert H KleinDepartment of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0002-7794-5753
Benjamin M KuterDepartment of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0002-2586-5129
Corey M GillDepartment of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0003-4494-1948
Mia BertalanDepartment of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0003-3519-7985
Brian ShawDepartment of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0003-2287-8204
Alexander KaplanDepartment of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0002-6668-309X
Megha SubramanianDepartment of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0002-4416-5128
Aarushi JainDepartment of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0002-8980-8350
Swaminathan KumarDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-9358-787X
Husain DanishDepartment of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York.ORCID 0000-0001-6581-2390
Michael WhiteDepartment of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0002-3855-9243
Osmaan ShahidDepartment of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-3694-8480
Kristen E PaukenDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-4309-7880
Brian C MillerDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-5931-4184
Dennie T FrederickDivision of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.ORCID 0000-0003-3355-5267
Christine HebertDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-7957-2604
McKenzie ShawDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0003-3734-5312
Maria Martinez-LageDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-5859-7562
Matthew FroschC. S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-3940-9861
Nancy WangDepartment of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0003-4350-296X
Elizabeth GerstnerMassachusetts General Hospital Cancer Center, Boston, Massachusetts.ORCID 0000-0003-2382-3838
Brian V NahedDepartment of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0001-8537-106X
William T CurryDepartment of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0002-8036-1847
Bob CarterDepartment of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0002-3586-1324
Daniel P CahillDepartment of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0003-2552-6546
Genevieve Marie BolandDivision of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-7522-6173
Benjamin IzarDivision of Hematology and Oncology, Columbia University Irving Medical Center, New York, New York.ORCID 0000-0003-2379-6702
Michael A DaviesDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-0977-0912
Arlene H SharpeDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-9736-2109
Mario L SuvàBroad Institute, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts.ORCID 0000-0001-9898-5351
Ryan J SullivanDepartment of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0001-5344-6645
Priscilla K Brastianos *Broad Institute, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts.ORCID 0000-0003-4470-8425
Scott L Carter *Broad Institute, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts.ORCID 0000-0002-8480-1475
Funding
Research Project 2 - Targeting Melanoma Tumor Survival and Apoptotic MachineryU54CA224070 · NCI · WISTAR INSTITUTE · PI Meenhard F Herlyn · 2017 to 2026
$13.9MThe University of Texas MD Anderson Cancer Center SPORE in MelanomaP50CA221703 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI YEE, CASSIAN · 2019 to 2023
$10.3MIdentification of genomic drivers of brain metastases in lung adenocarcinomaR01CA227156 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BRASTIANOS, PRISCILLA KALIOPI, CARTER, SCOTT · 2018 to 2022
$3.5MUsing MRI and circulating tumor DNA to improve the interpretation of response to immunotherapy and targeted therapy in CNS metastasesR01CA244975 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BRASTIANOS, PRISCILLA KALIOPI, GERSTNER, ELIZABETH · 2020 to 2024
$3.4MMechanisms of liver metastasis and associated resistance to immunotherapyR37CA258829 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Benjamin Izar · 2021 to 2026
$2.6MTargeting Unique Myeloid Populations to Overcome Anti-PD-1 Resistance Conferred by Specific Cancer MutationsK08CA248960 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MILLER, BRIAN C · 2020 to 2024
$1.2MIdentification of genomic drivers of brain metastases in renal cell carcinomaR21CA220253 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BRASTIANOS, PRISCILLA KALIOPI, CARTER, SCOTT · 2018 to 2019
$421kDissecting drug resistance in serial uveal melanoma biopsies using integrated, multi-modal single-cell profiling and novel machine learning tools.R21CA263381 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI IZAR, BENJAMIN · 2021 to 2022
$412kNCI NIH HHS K08 CA248960NCI NIH HHS P50 CA221703NCI NIH HHS R01 CA227156NCI NIH HHS R01 CA244975NCI NIH HHS R21 CA220253NCI NIH HHS R21 CA263381NCI NIH HHS R37 CA258829NCI NIH HHS U54 CA224070
Abstract
Melanoma-derived brain metastases (MBM) represent an unmet clinical need because central nervous system progression is frequently an end stage of the disease. Immune checkpoint inhibitors (ICI) provide a clinical opportunity against MBM; however, the MBM tumor microenvironment (TME) has not been fully elucidated in the context of ICI. To dissect unique elements of the MBM TME and correlates of MBM response to ICI, we collected 32 fresh MBM and performed single-cell RNA sequencing of the MBM TME and T-cell receptor clonotyping on T cells from MBM and matched blood and extracranial lesions. We observed myeloid phenotypic heterogeneity in the MBM TME, most notably multiple distinct neutrophil states, including an IL8-expressing population that correlated with malignant cell epithelial-to-mesenchymal transition. In addition, we observed significant relationships between intracranial T-cell phenotypes and the distribution of T-cell clonotypes intracranially and peripherally. We found that the phenotype, clonotype, and overall number of MBM-infiltrating T cells were associated with response to ICI, suggesting that ICI-responsive MBMs interact with peripheral blood in a manner similar to extracranial lesions. These data identify unique features of the MBM TME that may represent potential targets to improve clinical outcomes for patients with MBM.
Indexed as
Brain NeoplasmsMelanomaHumansImmune Checkpoint InhibitorsTumor MicroenvironmentImmune Checkpoint Inhibitors
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