Department of Oncology
BM BCh, MRCP, PhD
- Wellcome Intermediate Clinical Fellow
- Hon. Consultant Medical Oncologist
Checkpoint Immunotherapy has revolutionised the treatment of multiple cancer subtypes, notably melanoma.
Clinical outcomes from these treatments are variable however. Toxicity, in the form of immune related adverse events, is a frequent cause of patient morbidity, whilst many patients' tumours show only limited sensitivity to immunotherapy.
This inter-patient heterogeneity in response is determined by features of the cancer - such as driver mutations and overall mutational burden, as well as tumour-extrinsic factors. These include past immune exposures of the patient, genetically determined features of the immune system and other factors including potentially the microbiome (most notably the bacterial strains within the gut).
My group is interested in the interplay between patients' immune systems and their response to checkpoint immunotherapy. We study this in samples generously donated by cancer patients who have received treatment in the OUH.
We hope the findings of our work will further our understanding of how the immune system can tackle cancer, improving oncological outcomes from cancer immunotherapy whilst reduce suffering due to side effects.
IFNγ signaling in cytotoxic T cells restricts anti-tumor responses by inhibiting the maintenance and diversity of intra-tumoral stem-like T cells.
Mazet JM. et al, (2023), Nat Commun, 14
Germline variants associated with toxicity to immune checkpoint blockade.
Groha S. et al, (2022), Nat Med
IL7 genetic variation and toxicity to immune checkpoint blockade in patients with melanoma.
Taylor CA. et al, (2022), Nat Med
Genome-wide association study of leprosy in Malawi and Mali.
Gilchrist JJ. et al, (2022), PLoS Pathog, 18
Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity.
Gilchrist JJ. et al, (2022), Nat Commun, 13
Use of cemiplimab for advanced cutaneous squamous cell carcinoma: first real-world data from a UK perspective - a retrospective review
Nestor LA. et al, (2022), BRITISH JOURNAL OF DERMATOLOGY, 187, 107 - 108
A blood atlas of COVID-19 defines hallmarks of disease severity and specificity.
COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium. Electronic address: email@example.com None. and COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium None., (2022), Cell, 185, 916 - 938.e58
Phenotyping of cutaneous toxicities in patients with metastatic malignant melanoma treated with immune checkpoint blockade therapy at a UK tertiary care centre.
Ye W. et al, (2022), Clin Exp Dermatol, 47, 448 - 450
ACTR1A has pleiotropic effects on risk of leprosy, inflammatory bowel disease and atopy
Gilchrist J. et al, (2022)
An immunodominant NP105-113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease.
Peng Y. et al, (2022), Nat Immunol, 23, 50 - 61