Effects of oncolytic viruses on cell function in skin lymphoma

Dr. Egle Ramelyte

Universität Zürich
​​​​​​​Universitätsspital Zürich

Dr. Aizhan Tastanova

Universität Zürich
​​​​​​​Universitätsspital Zürich

Dr. Zsolt Balázs

Universität Zürich

For some years now, genetically engineered herpes viruses have been used to combat malignant cancer cells. Such “oncolytic viruses” have the capacity to penetrate tumour cells and destroy them. However, many questions on the mechanism underlying this strategy remain unanswered.

Egle Ramelyte, Aizhan Tastanova and Zsolt Balázs aimed to describe the molecular and cellular changes in such tumour cells infected with viruses in as much detail as possible. To this end, patients with primary cutaneous B-cell lymphoma were given local treatment with an injection of genetically engineered herpes virus (T-VEC). The researchers then took biopsies of treated and untreated tumour lesions. Minimally invasive sampling was carried out with a very fine needle to ensure that repeat samples could be taken at different points in time. This allowed a large number of single cell RNA analyses to be carried out and the effect of the viral treatment to be observed on a continuous basis at the cellular level for the first time. 

The results revealed that both the tumour cells and adjacent cells around the puncture site were infected with the viruses. This infection triggered an immune reaction that targeted the tumour and was detected far beyond the actual “infection focus”. Accordingly, destruction of the malignant cells was not only determined in the treated, but also in the untreated tumour lesions. A clinical effect of the treatment was determined in most patients.

This study allowed the results of an anti-tumour treatment to be analysed in a rapid and timely fashion, both at the molecular and cellular levels. In addition, the minimally invasive sampling technique with subsequent single cell analysis is exemplary, in that it gives us a significantly greater understanding of the biological mechanisms underlying oncolytic viral therapies.

Oncolytic virotherapy-mediated anti-tumor response: a single-cell perspective, Egle Ramelyte, Aizhan Tastanova, Zsolt Balázs, Desislava Ignatova, Patrick Turko, Ulrike Menzel, Emmanuella Guenova, Christian Beisel, Michael Krauthammer, Mitchell Paul Levesque, Reinhard Dummer. 
Cancer Cell. 2021 Mar 8;39(3):394-406.e4. doi: 10.1016/j.ccell.2020.12.022.