Millar, Fraser R;
Pennycuick, Adam;
Muir, Morwenna;
Quintanilla, Andrea;
Hari, Priya;
Freyer, Elisabeth;
Gautier, Philippe;
... Acosta, Juan Carlos; + view all
(2022)
Toll-like receptor 2 orchestrates a tumor suppressor response in non-small cell lung cancer.
Cell Reports
, 41
(6)
, Article 111596. 10.1016/j.celrep.2022.111596.
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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.
| Type: | Article |
|---|---|
| Title: | Toll-like receptor 2 orchestrates a tumor suppressor response in non-small cell lung cancer |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2022.111596 |
| Publisher version: | https://doi.org/10.1016/j.celrep.2022.111596 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | CP: Cancer, SASP, Toll-like receptor, cancer therapy, innate immune receptors, non-small cell lung cancer, premalignancy, senescence, senescence surveillance, tumor suppressor, Mice, Animals, Humans, Toll-Like Receptor 2, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Genes, Tumor Suppressor, Lung, Cellular Senescence |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10159803 |
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