Anatomy and Neuroscience - Research Publications

Permanent URI for this collection

http://hdl.handle.net/11343/181

Filters

2023 1
1
Reset filters

Settings
Statistics
Citations
Author: Antippa, Phillip × Author: Asselin-Labat, Marie-Liesse × Author: Irving, Louis × Author: Leong, Tracy Li-Tsein × Author: Steinfort, Daniel ×

Search Results

Now showing 1 - 1 of 1
  • Item
    No Preview Available
    Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer
    Weeden, CE ; Gayevskiy, V ; Marceaux, C ; Batey, D ; Tan, T ; Yokote, K ; Ribera, NT ; Clatch, A ; Christo, S ; Teh, CE ; Mitchell, AJ ; Trussart, M ; Rankin, LC ; Obers, A ; McDonald, JA ; Sutherland, KD ; Sharma, VJ ; Starkey, G ; D'Costa, R ; Antippa, P ; Leong, T ; Steinfort, D ; Irviing, L ; Swanton, C ; Gordon, CL ; Mackay, LK ; Speed, TP ; Gray, DHD ; Asselin-Labat, M-L (CELL PRESS, 2023-05-08)
    Tissue-resident memory T (TRM) cells provide immune defense against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts TRM activation and whether TRM cells existing in tissues before tumor onset influence cancer evolution in humans. We performed deep profiling of healthy lungs and lung cancers in never-smokers (NSs) and ever-smokers (ESs), finding evidence of enhanced immunosurveillance by cells with a TRM-like phenotype in ES lungs. In preclinical models, tumor-specific or bystander TRM-like cells present prior to tumor onset boosted immune cell recruitment, causing tumor immune evasion through loss of MHC class I protein expression and resistance to immune checkpoint inhibitors. In humans, only tumors arising in ES patients underwent clonal immune evasion, unrelated to tobacco-associated mutagenic signatures or oncogenic drivers. These data demonstrate that enhanced TRM-like activity prior to tumor development shapes the evolution of tumor immunogenicity and can impact immunotherapy outcomes.