An inhibitor of programmed death ligand 1 enhances natural killer cell-mediated immunity against malignant melanoma cells

• Published in: PloS one Vol. 16; no. 4; p. e0248870
• Main Authors: Lee, Young Shin, Heo, Woong, Choi, Ho-Jung, Cho, Hae-Ryung, Nam, Ji Ho, Ki, Yong Gan, Lee, Hong-Rae, Son, Woo-Chang, Park, You-Soo, Kang, Chi-Dug, Bae, Jaeho
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2021; Public Library of Science (PLoS)
• Subjects: Antibodies; Anticancer properties; Apoptosis; Auroral kilometric radiation; Biochemistry; Biology; Biology and life sciences; Bladder; Bladder cancer; Cancer; Care and treatment; Cell surface; Cell-mediated cytotoxicity; Cell-mediated immunity; CTLA-4 protein; Cytotoxicity; Drug dosages; Education; Experiments; Flow cytometry; Gene expression; Genetics; Head & neck cancer; Head and neck cancer; Health aspects; Immune response (cell-mediated); Immunity; Ionizing radiation; Killer cells; Ligands; Lung cancer; Lung diseases; Lymphocytes; Lymphocytes T; Medical research; Medicine; Medicine and Health Sciences; Melanoma; Methodology; Monoclonal antibodies; Natural killer cells; Non-small cell lung carcinoma; Oncology; Oncology, Experimental; Patients; PD-1 protein; PD-L1 protein; Penicillin; Physical Sciences; Physiological aspects; Radiation; Radiation therapy; Radiotherapy; Research and Analysis Methods; Research facilities; Science education; Side effects; Skin cancer; Small cell lung carcinoma; Squamous cell carcinoma; South Korea; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0248870

Since ionizing radiation has showed the dramatic effect to kill the cancer cells through direct DNA damage as well as triggering anti-cancer immune responses including induction of NKG2D ligands, it has used for long time to treat many cancer patients. However, it has been known that radiotherapy might promote the remnant cancer cells to escape immune system and metastasis. One of the suggested ways of immune evasion is induction of a ligand for programmed death-1 (PD-L1) in head and neck cancer, bladder cancer and lung cancer cells which engages the receptor, programmed death-1 (PD-1) in immune cells. PD-1/PD-L1 axis transduces the inhibitory signal and suppresses the adaptive immunity. However, their role in innate immunity remains poorly understood. Therefore, we investigated whether ionizing radiation could change the expression of PD-L1 in malignant melanoma cells and the receptor, programmed death-1 (PD-1), in NK-92 cells. Surface PD-L1 levels on melanoma cells were increased by ionizing radiation in a dose-independent manner but the level of PD-L1 was not changed significantly in NK-92 cells. Radiation-induced PD-L1 suppressed the activity of the NK-92 cells against melanoma cells despite of upregulation of NKG2D ligands. Furthermore, activated NK cells had high level of PD-1 and could not kill PD-L1+ melanoma cells effectively. When we used PD-L1 inhibitor or silenced PD-L1 gene, inhibited PD-1/PD-L1 axis reversed the activity of the suppressed NK cells. Through these results, we supposed that PD-1/PD-L1 blockade could enhance the immune responses of NK cells against melanoma cells after radiotherapy and might overcome the PD-L1 mediated radioresistance of cancer cells.