Health and disease are regulated, to a large extent, by our immune system. The immune system not only protects the body from infectious disease, but is involved in a number of conditions of increasing incidence and morbidity. In cancer, the immune system can be both cause and cure; it contributes to chronic inflammation that promotes tumour development, but it can also provide the ultimate weapon against metastatic disease. Thus, the development of ways to harness, direct or restrain immune responses has great potential for enhancing human health. QuanTII will address the need for new quantitative approaches to query immune cell function in lymphoid organs and tissues by developing novel quantitative methods of (1) the compartmentalisation and dynamics of T cells, (2) T cell receptor (TCR) repertoires in health and disease, in blood and tissues, and (3) T cell immunotherapies. Results from this project will improve our understanding of immunological memory, the variety of immune responses evoked by a single pathogen (immune repertoire), and the molecular and cellular mechanisms at the heart of cancer immunotherapies, such as adoptive cell transfer.
The specific training objectives of QuanTII are to provide an inspiring and supportive environment for the training of 15 ESRs, and to establish a broad programme of challenging research projects that are multidisciplinary and intersectoral, and lead to lasting, fruitful collaboration between ETN partners.
ESRs carried out research projects in immunological memory, immune repertoires, cancer and immunotherapies. Experimental approaches included sequencing and labelling of thymocytes and stem-cell memory T cells. Theoretical approaches included deterministic models of signalling, of T-cell subsets in exhaustion, and of the effect of checkpoint inhibitors. ESRs developed stochastic models of cell division and death, of the correlation structure of cell fates, and of the maintenance of product cell populations from progenitor cells, probabilistic repertoire models and agent-based models of heterogeneous populations. Modern algebraic and statistical techniques including Bayesian analysis were a feature. Once travel restrictions were relaxed, ESRs were able to undertake secondments and attend network meetings again. We are grateful that all QuanTII academic and industrial partners remained with the network from start to finish, participating in supervision of training and research, organising network events and hosting secondments.
