May 30, 2020

Harnessing natural killer immunity in metastatic small cell lung cancer

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
Sarah A BestKate D Sutherland


Small cell lung cancer (SCLC) is the most aggressive subtype of lung cancer and though most patients initially respond to platinum-based chemotherapy, resistance rapidly develops. Immunotherapy has promise in the treatment of lung cancer, however SCLC patients exhibit poor overall responses highlighting the necessity for alternative approaches. Natural killer (NK) cells are an alternative to T cell-based immunotherapies, that do not require sensitization to antigens presented on the surface of tumor cells. We investigated the immunophenotype of human SCLC tumors by both flow cytometry on fresh samples and bioinformatic analysis. Cell lines generated from murine SCLC were transplanted into mice lacking key cytotoxic immune cells. Subcutaneous tumor growth, metastatic dissemination and the activation of CD8+ T and NK cells were evaluated by histology and flow cytometry. Transcriptomic analysis of human SCLC tumors revealed heterogeneous immune checkpoint and cytotoxic signature profiles. Utilizing sophisticated genetically engineered mouse models, we demonstrated that the absence of NK cells, but not CD8+ T cells, significantly enhanced metastatic dissemination of SCLC tumor cells in vivo. Moreover, hyperactivation of NK cell act...Continue Reading

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Mentioned in this Paper

Fresh Specimen
Immune Effector Cell
Histology Procedure
Natural Killer Cells
Non-small Cell Lung Cancer Metastatic
Mouse Model
Malignant Neoplasm of Lung
Small Cell Carcinoma of Lung

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