An inhibitor of programmed death ligand 1 enhances natural killer cell-mediated immunity against malignant melanoma cells
| Autor: | Hong-Rae Lee, Hae-Ryung Cho, Woong Heo, Jae-Ho Bae, Young Shin Lee, Chi-Dug Kang, You-Soo Park, Woo-Chang Son, Ho-Jung Choi, Yong Gan Ki, Ji Ho Nam |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Skin Neoplasms Programmed Cell Death 1 Receptor Cancer Treatment NK cells Radiation Tolerance B7-H1 Antigen 0302 clinical medicine Cellular types Medicine and Health Sciences Melanoma Skin Tumors Immune Response Cultured Tumor Cells Immunity Cellular Multidisciplinary Radiation Chemistry Physics Immune cells Acquired immune system Killer Cells Natural medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Physical Sciences Medicine Melanoma Cells White blood cells Biological Cultures Research Article Clinical Oncology Cell biology Blood cells Science Immunology Radiation Therapy Dermatology Research and Analysis Methods Natural killer cell 03 medical and health sciences Immune system Radioresistance Cell Line Tumor medicine Humans Nuclear Physics Innate immune system Biology and life sciences Cancer Cancers and Neoplasms Cell Cultures medicine.disease 030104 developmental biology Animal cells Head and Neck Cancers Cancer cell Ionizing Radiation Cancer research Clinical Medicine |
| Zdroj: | PLoS ONE PLoS ONE, Vol 16, Iss 4, p e0248870 (2021) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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