Toll-like receptor orchestrates a tumor suppressor response in non-small cell lung cancer

Fraser Millar*, Adam Pennycuick, Morwenna Muir, Andrea Quintanilla, Priya Hari, Elisabeth Freyer, Philippe Gautier, Alison M Meynert, Graeme R Grimes, Carla Salomo Coll, Sofia Zdral, Stella Victorelli, Vitor H. Teixeira, John Connolly, Joao F Passos, Marian A Ros, William Wallace, Margaret C Frame, Andrew H Sims, Luke BoulterSam M Janes, Simon Wilkinson*, Juan Carlos Acosta*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Targeting early-stage lung cancer is vital to improve survival. Yet, the mechanisms and components of the early tumor suppressor response in lung cancer are not well understood. In this report we study the role of TLR2, a regulator of oncogene-induced senescence which is a key tumor suppressor response in premalignancy. Using human lung cancer samples and genetically engineered mouse models we show that TLR2 is active early in lung tumorigenesis where it correlates with improved survival and clinical regression.
Mechanistically, TLR2 impairs early lung cancer progression via activation of cell intrinsic cell cycle arrest pathways and the proinflammatory senescence-associated secretory phenotype (SASP). The SASP regulates non-cell autonomous anti-tumor responses such as immune surveillance of premalignant cells, and we observe impaired myeloid cell recruitment to lung tumors following Tlr2 loss. Lastly, we show that administration of a TLR2 agonist reduces lung tumor growth, highlighting TLR2 as a possible therapeutic target.
Original languageEnglish
JournalCell Reports
Early online date8 Nov 2022
Publication statusE-pub ahead of print - 8 Nov 2022


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