NK cell phenotypic modulation in lung cancer environment

• Published in: PloS one Vol. 9; no. 10; p. e109976
• Main Authors: Jin, Shi, Deng, Yi, Hao, Jun-Wei, Li, Yang, Liu, Bin, Yu, Yan, Shi, Fu-Dong, Zhou, Qing-Hua
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.10.2014; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Animals; Antigens; Antigens, Ly - biosynthesis; Biology and Life Sciences; Cancer; Cancer therapies; Cell culture; Cell survival; Coculture Techniques; Cytokines; Cytometry; Cytotoxicity; Disease-Free Survival; Down-regulation; Female; Flow cytometry; Gene Expression Regulation, Neoplastic; GPI-Linked Proteins - biosynthesis; Growth factors; Humans; Immunofluorescence; Immunological tolerance; Immunotherapy; Infiltration; Intercellular Signaling Peptides and Proteins - biosynthesis; Killer cells; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Laboratories; Lung cancer; Lung diseases; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Lung Neoplasms - therapy; Male; Medical prognosis; Medicine and Health Sciences; Metastases; Metastasis; Mice; Middle Aged; Natural killer cells; NK Cell Lectin-Like Receptor Subfamily C - biosynthesis; NKG2 antigen; Pathology; Patients; Prognosis; Receptor mechanisms; Receptors; Receptors, Immunologic - biosynthesis; Smoking; Spleen; Spleen - immunology; Spleen - metabolism; Surface markers; Tumor cells; Tumor Microenvironment - immunology; Tumors; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0109976

Nature killer (NK) cells play an important role in anti-tumor immunotherapy. But it indicated that tumor cells impacted possibly on NK cell normal functions through some molecules mechanisms in tumor microenvironment. Our study analyzed the change about NK cells surface markers (NK cells receptors) through immunofluorescence, flow cytometry and real-time PCR, the killed function from mouse spleen NK cell and human high/low lung cancer cell line by co-culture. Furthermore we certificated the above result on the lung cancer model of SCID mouse. We showed that the infiltration of NK cells in tumor periphery was related with lung cancer patients' prognosis. And the number of NK cell infiltrating in lung cancer tissue is closely related to the pathological types, size of the primary cancer, smoking history and prognosis of the patients with lung cancer. The expression of NK cells inhibitor receptors increased remarkably in tumor micro-environment, in opposite, the expression of NK cells activated receptors decrease magnificently. The survival time of lung cancer patient was positively related to NK cell infiltration degree in lung cancer. Thus, the down-regulation of NKG2D, Ly49I and the up-regulation of NKG2A may indicate immune tolerance mechanism and facilitate metastasis in tumor environment. Our research will offer more theory for clinical strategy about tumor immunotherapy.