Serial killing, addictive cytotoxicity and implications for immunotherapy

Serial killing, addictive cytotoxicity and implications for immunotherapy

Speaker: Professor Peter Friedl, Radboud University Nijmegen, Netherlands

Host: Elena Ortiz-Zapater

Cytotoxic T lymphocytes (CTL) eliminate tumour target cells in an antigen and cell-contact-dependent manner, both spontaneously and when activated by immunotherapy. Lethal hit delivery is considered to be a rapid and binary “yes/no” process under conditions of high immunogenicity, and killing enhancement may result from sequential conjugation of one CTL with multiple target cells, termed “serial killing”. I will show that the elimination of cancer cells results from a cooperative process executed by multiple CTL engaging sequentially with the same target cell. Migrating CTL transit between target cells and cooperate to initiate apoptosis by a series of sublethal interactions (additive cytotoxicity). The need for additive “hits” has implications for topographic mechanisms of immune evasion of tumour cells as well as immune intervention to enhance CTL accumulation and cooperation.