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    Isaac Othol

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Role of tertiary lymphoid structures (TLS) in anti-tumour response in melanoma and lung cancer

Student name

Isaac Othol (PhD candidate)

Supervisors

  1. Professor Elin Gray
  2. Dr Leslie Beasley

Summary of thesis

Melanoma and lung cancer remain major causes of cancer-related morbidity and mortality despite advances in immunotherapy, including immune checkpoint blockade (ICB). However, only a subset of patients achieves durable responses to ICB therapy, largely due to the immunosuppressive and heterogeneous nature of the tumour microenvironment (TME). Within the TME, tertiary lymphoid structures (TLS) emerge as ectopic lymphoid aggregates that form within or near tumours and are associated with improved responses to immunotherapy, although their precise role in anti-tumour immunity remains unclear. This study investigates how TLS formation and B-cell activity shape anti-tumour immune responses and influence immunotherapy success using murine models, spatial transcriptomics, and single-cell sequencing to characterise TLS and B-cell subpopulations and aims to identify blood-based biomarkers linked to TLS maturation.

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