Identification of peripheral markers of intra-tumoural tertiary lymphoid structures
Whilst checkpoint immunotherapy has revolutionised the treatment of cancer, only a subset of cancers, including melanoma, non-small cell lung cancer and renal cell carcinoma, respond to this treatment. Moreover, even in these cancer types there is marked heterogeneity in clinical benefit and the key determinants of therapeutic utility remain incompletely resolved.
It has recently been shown that the formation of tertiary lymphoid structures (TLS) within the tumour is associated with response to checkpoint immunotherapy, with increasing numbers of TLS having a more favourable outcome. This is intriguing because B cell responses were not thought to be central to clinical outcome in cancer immunotherapy. Indeed, it is unclear whether TLS formation is correlative of a favourable immune profile or instead, TLS play a causal role in outcome.
This project is designed to explore whether tumoural TLS form causal determinants of therapeutic response, and their interaction with other cell subsets. Specifically, the project will involve assessing TLS formation across pathological samples, integrating the results of this with a large dataset characterising immunological and transcriptomic parameters including B cell receptor sequencing performed across the same cohort.
You will be taught a mixture of computational and immunological approaches including handling of single cell sequencing data, analysis of T cell and B cell receptor data, flow cytometry and analysis of big datasets.