Oncolytic virotherapy-mediated anti-tumor response: a single-cell perspective
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2021-03-08
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Journal Article
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Abstract
Talimogene laherparepvec (T-VEC) is a genetically modified herpes simplex 1 virus (HSV-1) approved for cancer therapy. We investigate its effect on the clinical, histological, single-cell transcriptomic, and immune repertoire level using repeated fine-needle aspirates (FNAs) of injected and noninjected lesions in primary cutaneous B cell lymphoma (pCBCL). Thirteen patients received intralesional T-VEC, 11 of which demonstrate tumor response in the injected lesions. Using single-cell sequencing of the FNAs, we identify the malignant population and separate three pCBCL subtypes. Twenty-four hours after the injection, we detect HSV-1T-VEC transcripts in malignant and nonmalignant cells of the injected lesion but not of the noninjected lesion. Oncolytic virotherapy results in a rapid eradication of malignant cells. It also leads to interferon pathway activation and early influx of natural killer cells, monocytes, and dendritic cells. These events are followed by enrichment in cytotoxic T cells and a decrease of regulatory T cells in injected and noninjected lesions. © 2020 Elsevier
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published
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Journal / series
Volume
39 (3)
Pages / Article No.
394 - 4060000
Publisher
Cell Press
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Subject
oncolytic virotherapy; nonspecific cell infection; single-cell RNA sequencing; single-cell immune repertoire profiling; T-VEC-induced innate and adaptive immunity; primary cutaneous B cell lymphoma