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

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.

 Autoría: Millar F.R., Pennycuick A., Muir M., Quintanilla A., Hari P., Freyer E., Gautier P., Meynert A., Grimes G., Coll C.S., Zdral S., Victorelli S., Teixeira V.H., Connelly J., Passos J.F., Ros M.A., Wallace W.A.H., Frame M.C., Sims A.H., Boulter L., Janes S.M., Wilkinson S., Acosta J.C.,

 Fuente: Cell Reports, 2022, 41(6), 111596

 Editorial: Cell Press Elsevier

 Año de publicación: 2022

 Nº de páginas: 19

 Tipo de publicación: Artículo de Revista

 DOI: 10.1016/j.celrep.2022.111596

 ISSN: 2211-1247

 Proyecto español: PID2020-117860GB- 100

 Url de la publicación: https://doi.org/10.1016/j.celrep.2022.111596

Autoría

MILLAR, FRASER R

PENNYCUICK, ADAM

MUIR, MORWENNA

ANDREA QUINTANILLA CAVIA

HARI, PRIYA

FREYER, ELISABETH

GAUTIER, PHILIPPE

MEYNERT, ALISON

GRIMES, GRAEME

SALOMO COLL, CARLA

VICTORELLI, STELLA

TEIXEIRA, VITOR H

CONNELLY, JOHN

PASSOS, JOÃO F

MARIA ANGELES ROS LASIERRA

WALLACE, WILLIAM A H

FRAME, MARGARET C

SIMS, ANDREW H

JUAN CARLOS ACOSTA COBACHO