Dataset Information

CD56dim NK cell gene signature in melanoma patients with better and worse clinical outcomes

ABSTRACT: Natural killer (NK) cells are innate cytotoxic and immunoregulatory lymphocytes that have a central role in anti-tumor immunity and play a critical role in mediating cellular immunity in advanced cancer immunotherapies, such as dendritic cell (DC) vaccines. Our group recently tested a novel recombinant adenovirus-transduced autologous DC-based vaccine that simultaneously induces T cell responses against three melanoma-associated antigens for advanced melanoma patients. We examined the impact of this vaccine on the NK cell profile in melanoma patients. Relative immune cell population abundance was evaluated as previously described (Danaher et al. JITC, 2017). The abundance of the CD56dim NK cell gene signature was compared between pattients with better and worse outcome. Overall design: 41 lesions from 19 patients were excised at three different time-points during this trial and total RNA was extracted. Samples were profiled on the nCounter® MAX platform with the PanCancer Immune Profiling Panel

INSTRUMENT(S): NanoString nCounter human PanCancer Immune Profiling Panel (Custom Codeset)

ORGANISM(S): Homo sapiens

SUBMITTER: Lazar Vujanovic

PROVIDER: GSE124574 | GEO | 2019-01-03

REPOSITORIES: GEO

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Dataset's files

Source:

			Action	DRS
	GSE124574_RAW.tar	Raw
	GSE124574_melanoma_patients_CD56dim_cell_profiles.txt.gz	Txt
	filelist.txt	Txt

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Publications

CD56<sup>dim</sup> CD16<sup>-</sup> Natural Killer Cell Profiling in Melanoma Patients Receiving a Cancer Vaccine and Interferon-α.

Vujanovic Lazar L Chuckran Christopher C Lin Yan Y Ding Fei F Sander Cindy A CA Santos Patricia M PM Lohr Joel J Mashadi-Hossein Afshin A Warren Sarah S White Andy A Huang Alan A Kirkwood John M JM Butterfield Lisa H LH

Frontiers in immunology 20190129

Natural killer (NK) cells are innate cytotoxic and immunoregulatory lymphocytes that have a central role in anti-tumor immunity and play a critical role in mediating cellular immunity in advanced cancer immunotherapies, such as dendritic cell (DC) vaccines. Our group recently tested a novel recombinant adenovirus-transduced autologous DC-based vaccine that simultaneously induces T cell responses against three melanoma-associated antigens for advanced melanoma patients. Here, we examine the impac ...[more]

PMID: 30761123

Similar Datasets

Project description:Natural killer (NK) cells are innate cytotoxic and immunoregulatory lymphocytes that have a central role in anti-tumor immunity and play a critical role in mediating cellular immunity in advanced cancer immunotherapies, such as dendritic cell (DC) vaccines. Our group recently tested a novel recombinant adenovirus-transduced autologous DC-based vaccine that simultaneously induces T cell responses against three melanoma-associated antigens for advanced melanoma patients. Here, we examine the impact of this vaccine as well as the subsequent systemic delivery of high-dose interferon-?2b (HDI) on the circulatory NK cell profile in melanoma patients. At baseline, patient NK cells, particularly those isolated from high-risk patients with no measurable disease, showed altered distribution of CD56dim CD16+ and CD56dim CD16- NK cell subsets, as well as elevated serum levels of immune suppressive MICA, TN5E/CD73 and tactile/CD96, and perforin. Surprisingly, patient NK cells displayed a higher level of activation than those from healthy donors as measured by elevated CD69, NKp44 and CCR7 levels, and enhanced K562 killing. Elevated cytolytic ability strongly correlated with increased representation of CD56dim CD16+ NK cells and amplified CD69 expression on CD56dim CD16+ NK cells. While intradermal DC immunizations did not significantly impact circulatory NK cell activation and distribution profiles, subsequent HDI injections enhanced CD56bright CD16- NK cell numbers when compared to patients that did not receive HDI. Phenotypic analysis of tumor-infiltrating NK cells showed that CD56dim CD16- NK cells are the dominant subset in melanoma tumors. NanoString transcriptomic analysis of melanomas resected at baseline indicated that there was a trend of increased CD56dim NK cell gene signature expression in patients with better clinical response. These data indicate that melanoma patient blood NK cells display elevated activation levels, that intra-dermal DC immunizations did not effectively promote systemic NK cell responses, that systemic HDI administration can modulate NK cell subset distributions and suggest that CD56dim CD16- NK cells are a unique non-cytolytic subset in melanoma patients that may associate with better patient outcome.