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Updated: May 14, 2026

Evaluation of Tumor-infiltrating Leukocyte Subsets in a Subcutaneous Tumor Model
Published on: April 13, 2015
Lung tumor microenvironment induces specific gene expression signature in intratumoral NK cells
Mélanie Gillard-Bocquet1, Charles Caer, Nicolas Cagnard
1Centre de Recherche des Cordeliers, INSERM, U872 Paris, France ; Université Pierre et Marie Curie Paris, France ; Université Paris Descartes Paris, France.
Abstract:
Natural killer (NK) cells are able to recognize and kill tumor cells, however whether they contribute to tumor immunosurveillance is still debated. Our previous studies demonstrated the presence of NK cells in human lung tumors. Their comparison with NK cells from non-tumoral lung tissues and with blood NK cells from the same individuals revealed a decreased expression of some NK receptors and impaired ex vivo cytotoxic functions occurring specifically in NK cells isolated from the tumor microenvironment. The aim of the present study was to characterize the transcriptional profile of such intratumoral NK cells, by comparative microarray analysis of sorted NK cells isolated from non-tumoral (Non-Tum-NK) and tumoral (Tum-NK) lung tissues of 12 Non-Small Cell Lung Cancer patients. Our results reveal a specific gene expression signature of Tum-NK cells particularly in activation processes and cytotoxicity, confirming that tumor environment induces modifications in NK cells biology. Indeed, intratumoral NK cells display higher expression levels of NKp44, NKG2A, Granzymes A and K, and Fas mRNA. A particular pattern of receptors involved in chemotaxis was also observed, with an overexpression of CXCR5 and CXCR6, and a lower expression of CX3CR1 and S1PR1 genes in Tum-NK as compared to Non-Tum-NK cells. The precise identification of the molecular pathways modulated in the tumor environment will help to decipher the role of NK cells in tumor immunosurveillance and will open future investigations to manipulate their antitumoral functions.
Insights
Natural killer (NK) cells in lung tumors show altered gene expression, impacting their activation and cytotoxic functions. Understanding these changes is key to harnessing NK cell power against cancer.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Biology
Background:
- Natural killer (NK) cells are crucial for tumor immunosurveillance, but their role in lung cancer is debated.
- NK cells within the tumor microenvironment exhibit reduced receptor expression and impaired cytotoxic functions compared to those in healthy tissues or blood.
Purpose of the Study:
- To investigate the transcriptional profile of intratumoral NK cells in Non-Small Cell Lung Cancer (NSCLC).
- To identify specific gene expression signatures that characterize NK cells within the tumor microenvironment.
Main Methods:
- Comparative microarray analysis of sorted NK cells from tumoral (Tum-NK) and non-tumoral (Non-Tum-NK) lung tissues of 12 NSCLC patients.
- Analysis focused on gene expression related to NK cell activation, cytotoxicity, and chemotaxis.
Main Results:
- Intratumoral NK cells (Tum-NK) exhibit a distinct gene expression profile compared to non-tumoral NK cells (Non-Tum-NK).
- Tum-NK cells show increased mRNA levels of NKp44, NKG2A, Granzymes A and K, and Fas.
- Chemotaxis-related gene expression is altered in Tum-NK cells, with higher CXCR5/CXCR6 and lower CX3CR1/S1PR1 expression.
Conclusions:
- The tumor microenvironment significantly modifies NK cell biology, affecting their activation and cytotoxic potential.
- Identifying these molecular pathways provides insights into NK cell function in lung cancer and potential therapeutic targets.
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