Using genetically-engineered mouse models of lung cancer, several research groups, including Prof. Etienne Meylan's, have recently observed that neutrophils entering the tumor can have an increased lifespan compared to other neutrophils, a behaviour that endows them with tumor-supportive functions. Now, in a study published in EMBO Molecular Medicine, Etienne Meylan and his laboratory have identified the molecular mechanisms that enable neutrophils to survive long in the tumor. They revealed that a protein called Bcl-xL was upregulated in ageing tumor-associated neutrophils (TAN), and essential for their extended survival. By inhibiting this protein, the researchers were able to reduce TAN ageing, without disturbing normal neutrophils that express only little Bcl-xL. In the tumor, Bcl-xL blockade killed old TANs, which were replaced by younger ones. This is important, because among the young TANs there are certainly cells with anti-tumor capabilities. In response to treatment, tumor growth slowed down in a mouse model of lung adenocarcinoma. These results therefore demonstrate the feasibility to exploit a vulnerability of pro-tumor neutrophils, while preserving other neutrophils. More broadly, the targeting of select, tumor-supportive innate immune cells hold promise to enhance the efficacy of existing immunotherapies that usually target the adaptive immune system.
New publication on Tumor-associated Neutrophils
Using genetically-engineered mouse models of lung cancer, several research groups, including Prof. Etienne Meylan's, have recently observed that neutrophils entering the tumor can have an increased lifespan compared to other neutrophils, a behaviour that endows them with tumor-supportive functions. Now, in a study published in EMBO Molecular Medicine, Etienne Meylan and his laboratory have identified the molecular mechanisms that enable neutrophils to survive long in the tumor. They revealed that a protein called Bcl-xL was upregulated in ageing tumor-associated neutrophils (TAN), and essential for their extended survival. By inhibiting this protein, the researchers were able to reduce TAN ageing, without disturbing normal neutrophils that express only little Bcl-xL. In the tumor, Bcl-xL blockade killed old TANs, which were replaced by younger ones. This is important, because among the young TANs there are certainly cells with anti-tumor capabilities. In response to treatment, tumor growth slowed down in a mouse model of lung adenocarcinoma. These results therefore demonstrate the feasibility to exploit a vulnerability of pro-tumor neutrophils, while preserving other neutrophils. More broadly, the targeting of select, tumor-supportive innate immune cells hold promise to enhance the efficacy of existing immunotherapies that usually target the adaptive immune system.