Ramelyte, Tastanova, and Balázs et al. carried out a longitudinal study over a 91-day period in 13 patients with primary cutaneous B cell lymphoma, following intralesional treatment with oncolytic therapy (T-VEC). ScRNA seq (mRNA, BCR, TCR) of fine needle aspirates from injected skin lesions showed non-specific T-VEC uptake and replication in both non-malignant and malignant cell types. In both injected and non-injected lesions, a rapid decrease in malignant B cells occurred, with significant increases in NK cells, monocytes, CD8+ and CD4+ T cells, and cytotoxic marker expression in clonal vs. unique CD8+ T cells, suggesting remodeling of the TME and an adaptive response.
Contributed by Katherine Turner
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-1(T-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.
Author Info: (1) Dermatology Department, University Hospital Zurich and Medical Faculty, University of Zurich, 8091 Zurich, Switzerland. (2) Dermatology Department, University Hospital Zurich a
Author Info: (1) Dermatology Department, University Hospital Zurich and Medical Faculty, University of Zurich, 8091 Zurich, Switzerland. (2) Dermatology Department, University Hospital Zurich and Medical Faculty, University of Zurich, 8091 Zurich, Switzerland. (3) Department of Quantitative Biomedicine, University of Zurich, 8057 Zurich, Switzerland; Biomedical Informatics, University Hospital of Zurich, 8057 Zurich, Switzerland. (4) Dermatology Department, University Hospital Zurich and Medical Faculty, University of Zurich, 8091 Zurich, Switzerland; Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland. (5) Dermatology Department, University Hospital Zurich and Medical Faculty, University of Zurich, 8091 Zurich, Switzerland. (6) Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland. (7) Dermatology Department, University Hospital Zurich and Medical Faculty, University of Zurich, 8091 Zurich, Switzerland; Department of Dermatology, Lausanne University Hospital (CHUV) and Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland. (8) Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland. (9) Department of Quantitative Biomedicine, University of Zurich, 8057 Zurich, Switzerland; Biomedical Informatics, University Hospital of Zurich, 8057 Zurich, Switzerland. (10) Dermatology Department, University Hospital Zurich and Medical Faculty, University of Zurich, 8091 Zurich, Switzerland. (11) Dermatology Department, University Hospital Zurich and Medical Faculty, University of Zurich, 8091 Zurich, Switzerland. Electronic address: reinhard.dummer@usz.ch.
