The 2022 Chappel Lecture will be presented by Dr. Laszlo Radvanyi, President and Scientific Director of the Ontario Institute for Cancer Research (OICR). The annual Chappel Lecture was established by 1950 OVC graduate Clifford Chappel in memory of his father, to give students and faculty the opportunity to meet internationally known scientists.

Modulation of the Immune Response in Cancer by Retroelements and Endogenous Retroviruses: New Targets for Immunotherapy

This lecture will describe how otherwise silent, non-coding regions of the human genome containing retroelements (REs) and human endogenous retroviruses (HERVs) are activated in human cancer and their implications. New findings in previous work, as well as recent work in Dr. Radvanyi’s lab and his international collaborative team, have found that REs and HERVs are induced in multiple cancer types and can be a source of tumour antigens triggering de novo immune responses in patients that may also be harnessed as a new target for immunotherapy. On the flip-side however, expression of these REs and HERVs in tumours can also disrupt normal immunoregulation. Recent results have found that in both pediatric and adult cancers, aberrant transcription at pericentromeric regions of chromosomes lead to the expression and secretion of RNA from REs (including LINE, SINE and HSAT) and HERVs in extracellular vesicles (EVs) that infect stromal cells and myeloid cells both in the tumour microenvironment and systemically in the body. These EVs are taken up by host cells driving DNA damage and induction of immunosuppressive innate inflammatory responses disrupting normal cellular differentiation and function of macrophages and dendritic cells. Thus, these EVs seem to be long-distance, systemic “immune disruptors” in cancer patients and alleviating this systemic immune-dysregulation may represent a new challenge and opportunity in cancer immunotherapy.

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