| First Author | Weeden CE | Year | 2023 |
| Journal | Cancer Cell | Volume | 41 |
| Issue | 5 | Pages | 837-852.e6 |
| PubMed ID | 37086716 | Mgi Jnum | J:336848 |
| Mgi Id | MGI:7470584 | Doi | 10.1016/j.ccell.2023.03.019 |
| Citation | Weeden CE, et al. (2023) Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer. Cancer Cell |
| abstractText | Tissue-resident memory T (T(RM)) cells provide immune defense against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts T(RM) activation and whether T(RM) 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 T(RM)-like phenotype in ES lungs. In preclinical models, tumor-specific or bystander T(RM)-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 T(RM)-like activity prior to tumor development shapes the evolution of tumor immunogenicity and can impact immunotherapy outcomes. |
