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Discovery of specialized NK cell populations infiltrating human melanoma metastases
Lucas Ferrari de Andrade, … , Guo-Cheng Yuan, Kai W. Wucherpfennig
Lucas Ferrari de Andrade, … , Guo-Cheng Yuan, Kai W. Wucherpfennig
Published December 5, 2019
Citation Information: JCI Insight. 2019;4(23):e133103. https://doi.org/10.1172/jci.insight.133103.
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Research Article Immunology Oncology

Discovery of specialized NK cell populations infiltrating human melanoma metastases

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Abstract

NK cells contribute to protective antitumor immunity, but little is known about the functional states of NK cells in human solid tumors. To address this issue, we performed single-cell RNA-seq analysis of NK cells isolated from human melanoma metastases, including lesions from patients who had progressed following checkpoint blockade. This analysis identified major differences in the transcriptional programs of tumor-infiltrating compared with circulating NK cells. Tumor-infiltrating NK cells represented 7 clusters with distinct gene expression programs indicative of significant functional specialization, including cytotoxicity and chemokine synthesis programs. In particular, NK cells from 3 clusters expressed high levels of XCL1 and XCL2, which encode 2 chemokines known to recruit XCR1+ cross-presenting DCs into tumors. In contrast, NK cells from 2 other clusters showed a higher level of expression of cytotoxicity genes. These data reveal key features of NK cells in human tumors and identify NK cell populations with specialized gene expression programs.

Authors

Lucas Ferrari de Andrade, Yuheng Lu, Adrienne Luoma, Yoshinaga Ito, Deng Pan, Jason W. Pyrdol, Charles H. Yoon, Guo-Cheng Yuan, Kai W. Wucherpfennig

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Figure 1

Isolation and scRNA-seq characterization of NK cells from human melanoma metastases and matching blood samples.

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Isolation and scRNA-seq characterization of NK cells from human melanoma...
(A) Gating strategy for the isolation of NK cells from blood and melanoma metastasis from patient CY158 by flow cytometry. (B) Percentage of blood (left) and tumor-infiltrating lymphocytes (right) from multiple patients that were NK cells (after exclusion of myeloid cells). (C) Comparison of NK cell clusters in blood versus melanoma metastasis (patient CY158) by scRNA-seq. UMAP plots were used to visualize blood and tumor-infiltrating NK cell clusters, and the percentage of NK cells in each cluster is indicated for blood and tumor NK cells (left). NK cell clusters are color coded, and key differentially expressed genes are shown for each cluster (right).

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