STK11/LKB1 Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact

The STK11/LKB1 gene codes for liver kinase B1 (STK11/LKB1), a highly conserved serine/threonine kinase involved in many energy-related cellular processes. The canonical tumor-suppressive role for STK11/LKB1 involves the activation of AMPK-rela...

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Autores principales:	Elvire Pons-Tostivint, Alexandre Lugat, Jean-François Fontenau, Marc Guillaume Denis, Jaafar Bennouna
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>STK11/LKB1</i> non-small cell lung cancer immunotherapy biomarker KRAS Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6e838efed2924f16aa464fddfa4762ff
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spelling	oai:doaj.org-article:6e838efed2924f16aa464fddfa4762ff2021-11-25T17:11:50Z<i>STK11/LKB1</i> Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact10.3390/cells101131292073-4409https://doaj.org/article/6e838efed2924f16aa464fddfa4762ff2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3129https://doaj.org/toc/2073-4409The <i>STK11/LKB1</i> gene codes for liver kinase B1 (<i>STK11/LKB1</i>), a highly conserved serine/threonine kinase involved in many energy-related cellular processes. The canonical tumor-suppressive role for <i>STK11/LKB1</i> involves the activation of AMPK-related kinases, a master regulator of cell survival during stress conditions. In pre-clinical models, inactivation of <i>STK11/LKB1</i> leads to the progression of lung cancer with the acquisition of metastatic properties. Moreover, preclinical and clinical data have shown that inactivation of <i>STK11/LKB1</i> is associated with an inert tumor immune microenvironment, with a reduced density of infiltrating cytotoxic CD8<sup>+</sup> T lymphocytes, a lower expression of PD-(L)1, and a neutrophil-enriched tumor microenvironment. In this review, we first describe the biological function of <i>STK11/LKB1</i> and the role of its inactivation in cancer cells. We report descriptive epidemiology, co-occurring genomic alterations, and prognostic impact for lung cancer patients. Finally, we discuss recent data based on pre-clinical models and lung cancer cohorts analyzing the results of <i>STK11/LKB1</i> alterations on the immune system and response or resistance to immune checkpoint inhibitors.Elvire Pons-TostivintAlexandre LugatJean-François FontenauMarc Guillaume DenisJaafar BennounaMDPI AGarticle<i>STK11/LKB1</i>non-small cell lung cancerimmunotherapybiomarkerKRASBiology (General)QH301-705.5ENCells, Vol 10, Iss 3129, p 3129 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>STK11/LKB1</i> non-small cell lung cancer immunotherapy biomarker KRAS Biology (General) QH301-705.5
spellingShingle	<i>STK11/LKB1</i> non-small cell lung cancer immunotherapy biomarker KRAS Biology (General) QH301-705.5 Elvire Pons-Tostivint Alexandre Lugat Jean-François Fontenau Marc Guillaume Denis Jaafar Bennouna <i>STK11/LKB1</i> Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact
description	The <i>STK11/LKB1</i> gene codes for liver kinase B1 (<i>STK11/LKB1</i>), a highly conserved serine/threonine kinase involved in many energy-related cellular processes. The canonical tumor-suppressive role for <i>STK11/LKB1</i> involves the activation of AMPK-related kinases, a master regulator of cell survival during stress conditions. In pre-clinical models, inactivation of <i>STK11/LKB1</i> leads to the progression of lung cancer with the acquisition of metastatic properties. Moreover, preclinical and clinical data have shown that inactivation of <i>STK11/LKB1</i> is associated with an inert tumor immune microenvironment, with a reduced density of infiltrating cytotoxic CD8<sup>+</sup> T lymphocytes, a lower expression of PD-(L)1, and a neutrophil-enriched tumor microenvironment. In this review, we first describe the biological function of <i>STK11/LKB1</i> and the role of its inactivation in cancer cells. We report descriptive epidemiology, co-occurring genomic alterations, and prognostic impact for lung cancer patients. Finally, we discuss recent data based on pre-clinical models and lung cancer cohorts analyzing the results of <i>STK11/LKB1</i> alterations on the immune system and response or resistance to immune checkpoint inhibitors.
format	article
author	Elvire Pons-Tostivint Alexandre Lugat Jean-François Fontenau Marc Guillaume Denis Jaafar Bennouna
author_facet	Elvire Pons-Tostivint Alexandre Lugat Jean-François Fontenau Marc Guillaume Denis Jaafar Bennouna
author_sort	Elvire Pons-Tostivint
title	<i>STK11/LKB1</i> Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact
title_short	<i>STK11/LKB1</i> Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact
title_full	<i>STK11/LKB1</i> Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact
title_fullStr	<i>STK11/LKB1</i> Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact
title_full_unstemmed	<i>STK11/LKB1</i> Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact
title_sort	<i>stk11/lkb1</i> modulation of the immune response in lung cancer: from biology to therapeutic impact
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6e838efed2924f16aa464fddfa4762ff
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<i>STK11/LKB1</i> Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact

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