Details

Autor(en) / Beteiligte

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

Titel

Toll-like receptor 2 orchestrates a tumor suppressor response in non-small cell lung cancer

Ist Teil von

• Cell reports (Cambridge), 2022-11, Vol.41 (6), p.111596, Article 111596

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •TLR2 is associated with improved survival and premalignant regression in NSCLC•TLR2 mediates oncogene-induced senescence and the SASP in early lung tumors•The Tlr2-mediated SASP recruits myeloid cells and promotes senescence surveillance•Targeting Tlr2 therapeutically reduces lung tumor growth in mouse models Millar et al. show that TLR2 is expressed in early lung cancer, where it is associated with improved survival and clinical regression. Using mouse models, they show that Tlr2 regulates growth arrest pathways and anti-tumoral immune surveillance. Targeting Tlr2 activity with an agonist significantly reduces early lung tumor growth.