Natural killer cells as immunotherapy to target rapidly evolving non-small cell lung carcinoma

Abstract

Non-small cell lung carcinoma (NSCLC) is a hard-to-treat, high mortality cancer in need of more effective therapy options. Natural killer (NK) cells are innate lymphocytes that contribute to anti-tumor functions through direct cell lysis and cytokine release. NK cells may be adoptively transferred or recruited for therapy, but treatment-induced phenotypic evolution of tumor surface proteins challenge selection of the ideal cell subsets. We studied how surface proteins interacting with NK cells on A549 cells evolve in response to inflammation, interaction with immune cells, chemotherapy, and radiation. Our results revealed dynamic, transient changes that implicate different NK cell subsets as ideal tumor killers. Analysis of responding NK cell populations against treated A549 cells, and antibody-mediated blockade experiments revealed that inhibitory interactions dominantly suppress activation driven through activating receptor-ligand binding. We conclude understanding evolving tumor phenotypes allows for selection of ideal NK cell killers to complement existing and nascent treatment approaches.