<i>STK11/LKB1</i> Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact
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-rela...
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| Autores principales: | , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/6e838efed2924f16aa464fddfa4762ff |
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| Sumario: | 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. |
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