Egle Ramelyte, Aizhan Tastanova, Zsolt Balázs, Desislava Ignatova, Patrick Turko, Ulrike Menzel, Emmanuella Guenova, Christian Beisel, Michael Krauthammer, Mitchell Paul Levesque, Reinhard Dummer
*CCCZ Members in bold
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.
Reinhard Dummer, professor at the University of Zurich and Department of Dermatology at the University Hospital Zurich:
“Combining minimally invasive sampling techniques and advanced sequencing technologies allows insights in earliest cancer therapy induced changes on a single cell level and potentially optimize treatment approaches in cancer patients ”