@article{10902/27270,
year = {2022},
url = {https://hdl.handle.net/10902/27270},
abstract = {Targeting early-stage lung cancer is vital to improve survival. However, 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 Toll-like receptor 2 (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 after Tlr2 loss. Last, we show that administration of a TLR2 agonist reduces lung tumor growth, highlighting TLR2 as a possible therapeutic target.},
organization = {Funding: F.R.M. is funded by a Wellcome Trust clinical research fellowship through the Edinburgh Clinical Academic Track (ECAT) program (203913/Z/16/Z), a Wellcome Trust-ISSF3 award (IS3-R1.07 20/21), and a Wellcome Trust iTPA award (209710/Z/17/Z). J.C.A. core lab funding was received from Cancer Research UK (C47559/A16243, Training and Career Development Board – Career Development Fellowship), the University of Edinburgh (Chancellor’s Fellowship), and the Ministry of Science and Innovation of the Government of Spain (Proyecto PID2020-117860GB-100 financiado por MCIN/AEI/10.13039/501100011033). S.W. is supported by a Cancer Research UK senior fellowship (A29576). J.C. is supported by a

Wellcome Trust clinical lectureship through the ECAT program (203913/Z/16/Z). M.M. is supported by a CRUK Edinburgh Centre Award (C157/A25140). S.V. and J.F.P. are funded by National Institute on Aging (NIA) grants (R01AG 68048-1 and UG3CA 268103-1).},
publisher = {Cell Press Elsevier},
publisher = {Cell Reports, 
2022, 41(6), 111596},
title = {Toll-like receptor 2 orchestrates a tumor suppressor response in non-small cell lung cancer},
author = {Millar, Fraser R and Pennycuick, Adam and Muir, Morwenna and Quintanilla Cavia, Andrea and Hari, Priya and Freyer, Elisabeth and Gautier, Philippe and Meynert, Alison and Grimes, Graeme and Salomo Coll, Carla and Zdral Noguero, Sofía  and Victorelli, Stella and Teixeira, Vitor H and Connelly, John and Passos, João F and Ros Lasierra, María Ángeles and Wallace, William A H and Frame, Margaret C and Sims, Andrew H and Acosta Cobacho, Juan Carlos},
}