Invited Speaker Asia-Pacific Vaccine and Immunotherapy Congress 2023

Early immune pressure initiated by tissue-resident memory T cells sculpts tumour evolution in non-small cell lung cancer (#37)

Marie-Liesse Asselin-Labat 1
  1. Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia

Tissue-resident memory T cells (TRM) provide immune defence against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts TRM activation and whether pre-existing TRM influence tumour evolution in humans. We performed deep profiling of healthy lungs and lung cancers in never-smokers (NS) and ever-smokers (ES), finding evidence of enhanced TRM immunosurveillance in ES lungs. In preclinical models, tumour-specific or bystander TRM present prior to tumour onset boosted immune cell recruitment, causing tumour immune evasion through loss of MHC Class I protein expression, and resistance to immune checkpoint inhibitors. In humans, only tumours arising in ES patients underwent clonal immune evasion, indicative of early immune escape. These data demonstrate that enhanced TRM activity prior to tumour development shapes the evolution of tumour immunogenicity and can impact immunotherapy outcomes.