Dissecting the Determinants of Response to Checkpoint Inhibitors
Cancer treatment is being revolutionised by checkpoint inhibitor immunotherapy (CKI). In melanoma, where there is limited role for radiotherapy or chemotherapy, CKI forms the frontline treatment. Across many other cancer subtypes, including lung, bladder, renal and nasopharyngeal, CKIs are similarly becoming standard treatments.
The response to CKI is dependent upon tumour genetics and host immunity. For example, the ability to present tumour antigen is determined by HLA type. Similarly, antigens need to be recognised by T-cell receptors and multiple polymorphisms determine the gene usage within T-cell receptors. Notably, effective immunity depends upon overall immune health – the ageing immune system undergoes skewing of myeloid:lymphoid cell subset ratios, becoming more pro-inflammatory. Finally, chronic infections such as EBV and CMV can place additional demands upon the immune system that may impact CKI treatment.
This project will seek to explore these aspects in samples from a large cohort of melanoma patients our group is working with.
The techniques used will be tailored to this project but include standard immunological and genetic techniques such as multi-colour flow cytometry and single cell sequencing. Additionally the student will receive training in computational analysis so that they can perform analysis of large genomic datasets independently.