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

Elvire Pons-Tostivint 1, 2 Alexandre Lugat 3 Jean-François Fonteneau 1 Marc Guillaume Denis 2 Jaafar Bennouna 1, 4 
1 CRCINA-ÉQUIPE 4 - Immunogenic Cell Death and Mesothelioma Therapy
CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
3 CRCINA-ÉQUIPE 13 - Nuclear Oncology
CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
Abstract : 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-related kinases, a master regulator of cell survival during stress conditions. In pre-clinical models, inactivation of STK11/LKB1 leads to the progression of lung cancer with the acquisition of metastatic properties. Moreover, preclinical and clinical data have shown that inactivation of STK11/LKB1 is associated with an inert tumor immune microenvironment, with a reduced density of infiltrating cytotoxic CD8+ 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 STK11/LKB1 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 STK11/LKB1 alterations on the immune system and response or resistance to immune checkpoint inhibitors.
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https://www.hal.inserm.fr/inserm-03546835
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Submitted on : Friday, January 28, 2022 - 10:51:23 AM
Last modification on : Wednesday, April 27, 2022 - 3:47:19 AM
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Elvire Pons-Tostivint, Alexandre Lugat, Jean-François Fonteneau, Marc Guillaume Denis, Jaafar Bennouna. STK11/LKB1 Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact. Cells, MDPI, 2021, 10 (11), pp.3129. ⟨10.3390/cells10113129⟩. ⟨inserm-03546835⟩

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