Characterising CD8+ T Cell Responses in Non-Small-Cell Lung Cancer
Before joining the Dong group, I completed my BSc in Biomedical Sciences with a Year in Industry at the University of York, obtaining First-Class Honours with Distinction. For my final-year project, I was involved with investigating the potential role of RNA methylation in the upregulation of PD-L1 as part of the Lagos group. I spent a year working in GlaxoSmithKline's BioPharm Discovery department where I investigated next-generation bispecific antibody formats with potential oncological applications and published my first paper (albeit a review).
My research in the Dong group is focused on characterising and understanding CD8+ T cell responses in the NSCLC microenvironment at a single-cell resolution, using a combination of ex vivo scRNA/TCR-seq and paired in vitro expanded T cell clones. We are especially interested in tumor-reactive clonotypes that lack expression of the inhibitory receptor PD-1, or are specific for 'Cancer Testis Antigens', hypothesising that these two populations will overlap. We hope to identify a population of tumour-reactive TILs that lack canonical markers of exhaustion ex vivo yet display high cytotoxic and proliferative capabilities in vitro, suggesting the potential to mediate tumour control. Such a population may have improved therapeutic outcome when used for adoptive cell transfer compared to non-specifically expanded TILs, analogous to CD69- CD39- TILs described by the Rosenberg group (Krishna et al, 2021), and act as a prognostic marker and predictor of response to immune checkpoint blockade, similar to the TCF-1+ 'progenitor exhausted' CD8+ T cells in melanoma recently described by several groups (Feldman et al, 2018; Siddiqui et al, 2019; Li et al, 2019; Chen et al 2019).