American Association for Cancer Research
Browse
10780432ccr211694-sup-265392_1_supp_7116076_qt218p.xlsx (9.61 kB)

Supplementary Table 1 from Single-Cell Characterization of the Immune Microenvironment of Melanoma Brain and Leptomeningeal Metastases

Download (9.61 kB)
dataset
posted on 2023-03-31, 22:46 authored by Inna Smalley, Zhihua Chen, Manali Phadke, Jiannong Li, Xiaoqing Yu, Clayton Wyatt, Brittany Evernden, Jane L. Messina, Amod Sarnaik, Vernon K. Sondak, Chaomei Zhang, Vincent Law, Nam Tran, Arnold Etame, Robert J.B. Macaulay, Zeynep Eroglu, Peter A. Forsyth, Paulo C. Rodriguez, Y. Ann Chen, Keiran S.M. Smalley

Supplemental Table 1: Flow Cytometry Antibodies

Funding

NIH

Department of Defense

Melanoma Research Foundation

Moffitt DRP Innovation Core Project Award

NCI

Moffitt Foundation

History

ARTICLE ABSTRACT

Melanoma brain metastases (MBM) and leptomeningeal melanoma metastases (LMM) are two different manifestations of melanoma CNS metastasis. Here, we used single-cell RNA sequencing (scRNA-seq) to define the immune landscape of MBM, LMM, and melanoma skin metastases. scRNA-seq was undertaken on 43 patient specimens, including 8 skin metastases, 14 MBM, and 19 serial LMM specimens. Detailed cell type curation was performed, the immune landscapes were mapped, and key results were validated by IHC and flow cytometry. Association analyses were undertaken to identify immune cell subsets correlated with overall survival. The LMM microenvironment was characterized by an immune-suppressed T-cell landscape distinct from that of brain and skin metastases. An LMM patient with long-term survival demonstrated an immune repertoire distinct from that of poor survivors and more similar to normal cerebrospinal fluid (CSF). Upon response to PD-1 therapy, this extreme responder showed increased levels of T cells and dendritic cells in their CSF, whereas poor survivors showed little improvement in their T-cell responses. In MBM patients, therapy led to increased immune infiltrate, with similar T-cell transcriptional diversity noted between skin metastases and MBM. A correlation analysis across the entire immune landscape identified the presence of a rare population of dendritic cells (DC3) that was associated with increased overall survival and positively regulated the immune environment through modulation of activated T cells and MHC expression. Our study provides the first atlas of two distinct sites of melanoma CNS metastases and defines the immune cell landscape that underlies the biology of this devastating disease.

Usage metrics

    Clinical Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC