Microenvironmental Landscape of Human Melanoma Brain Metastases in Response to Immune Checkpoint Inhibition-Reference-Cited by-同舟云学术

Microenvironmental Landscape of Human Melanoma Brain Metastases in Response to Immune Checkpoint Inhibition

Published:2022-06-15 Issue:8 Volume:10 Page:996-1012
ISSN:2326-6066
Container-title:Cancer Immunology Research
language:en
Short-container-title:

Author:

Alvarez-Breckenridge Christopher¹²^ORCID,Markson Samuel C.³⁴⁵⁶^ORCID,Stocking Jackson H.⁷^ORCID,Nayyar Naema⁷^ORCID,Lastrapes Matt⁵⁶⁸^ORCID,Strickland Matthew R.⁷⁹^ORCID,Kim Albert E.⁷⁹^ORCID,de Sauvage Magali⁷^ORCID,Dahal Ashish⁷^ORCID,Larson Juliana M.⁷^ORCID,Mora Joana L.⁵⁶⁹^ORCID,Navia Andrew W.¹⁰¹¹¹²¹³^ORCID,Klein Robert H.⁷^ORCID,Kuter Benjamin M.⁷^ORCID,Gill Corey M.⁷^ORCID,Bertalan Mia⁷^ORCID,Shaw Brian⁷^ORCID,Kaplan Alexander⁷^ORCID,Subramanian Megha⁷^ORCID,Jain Aarushi⁷^ORCID,Kumar Swaminathan¹⁴^ORCID,Danish Husain¹⁵¹⁶^ORCID,White Michael⁷^ORCID,Shahid Osmaan⁶^ORCID,Pauken Kristen E.³⁴^ORCID,Miller Brian C.³⁴⁵¹⁷^ORCID,Frederick Dennie T.¹⁸^ORCID,Hebert Christine¹⁹^ORCID,Shaw McKenzie¹⁹^ORCID,Martinez-Lage Maria¹⁹^ORCID,Frosch Matthew²⁰^ORCID,Wang Nancy⁷^ORCID,Gerstner Elizabeth⁹^ORCID,Nahed Brian V.²^ORCID,Curry William T.²^ORCID,Carter Bob²^ORCID,Cahill Daniel P.²^ORCID,Boland Genevieve Marie¹⁸^ORCID,Izar Benjamin²¹²²^ORCID,Davies Michael A.¹⁴^ORCID,Sharpe Arlene H.³⁴⁵^ORCID,Suvà Mario L.⁵¹⁹^ORCID,Sullivan Ryan J.⁷⁹^ORCID,Brastianos Priscilla K.⁵⁷⁹^ORCID,Carter Scott L.⁵⁶^ORCID

Affiliation:

1. 1Departments of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

2. 2Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.

3. 3Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts.

4. 4Evergrande Center for Immunological Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts.

5. 5Broad Institute, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts.

6. 6Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts.

7. 7Department of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.

8. 8Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

9. 9Massachusetts General Hospital Cancer Center, Boston, Massachusetts.

10. 10Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts.

11. 11Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, Massachusetts.

12. 12Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.

13. 13Ragon Institute, Harvard University, Massachusetts Institute of Technology, and Massachusetts General Hospital, Cambridge, Massachusetts.

14. 14Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

15. 15Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York.

16. 16Weill Cornell Medical Center, New York, New York.

17. 17Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

18. 18Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

19. 19Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

20. 20C. S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

21. 21Division of Hematology and Oncology, Columbia University Irving Medical Center, New York, New York.

22. 22Columbia Center for Translational Immunology, New York, New York.

Abstract

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.

Funder

Damon Runyon Cancer Research Foundation Melanoma Research Alliance Breast Cancer Research Foundation

NIH

NCI NIH

Adelson Medical Research Foundation Melanoma Foundation NIH NCI

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Immunology

Link

https://aacrjournals.org/cancerimmunolres/article-pdf/doi/10.1158/2326-6066.CIR-21-0870/3161823/cir-21-0870.pdf

Reference67 articles.