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Tim-3 Expression by Peripheral Natural Killer Cells and Natural Killer T Cells Increases in Patients with Lung Cancer - Reduction after Surgical Resection

  • Xu, Li-Yun (Cell and Molecular Biology Laboratory, Zhoushan Hospital) ;
  • Chen, Dong-Dong (Cell and Molecular Biology Laboratory, Zhoushan Hospital) ;
  • He, Jian-Ying (Cell and Molecular Biology Laboratory, Zhoushan Hospital) ;
  • Lu, Chang-Chang (Lung Cancer Research Center of Zhoushan, Zhoushan Hospital) ;
  • Liu, Xiao-Guang (Cell and Molecular Biology Laboratory, Zhoushan Hospital) ;
  • Le, Han-Bo (Department of Cardio-Thoracic Surgery, Zhoushan Hospital) ;
  • Wang, Chao-Ye (Department of Cardio-Thoracic Surgery, Zhoushan Hospital) ;
  • Zhang, Yong-Kui (Lung Cancer Research Center of Zhoushan, Zhoushan Hospital)
  • 발행 : 2014.12.18

초록

Background: The purpose of this study was to investigate Tim-3 expression on peripheral CD3-CD56+ natural killer (NK) cells and CD3+CD56+ natural killer T (NKT) cells in lung cancer patients. Materials and Methods: We analyzed Tim-3+CD3-CD56+ cells, Tim-3+CD3-$CD56^{dim}$ cells, Tim-3+CD3-$CD56^{bright}$ cells, and Tim-3+CD3+CD56+ cells in fresh peripheral blood from 79 lung cancer cases preoperatively and 53 healthy controls by flow cytometry. Postoperative blood samples were also analyzed from 21 members of the lung cancer patient cohort. Results: It was showed that expression of Tim-3 was significantly increased on CD3-CD56+ cells, CD3-$CD56^{dim}$ cells and CD3+CD56+ cells in lung cancer patients as compared to healthy controls (p=0.03, p=0.03 and p=0.04, respectively). When analyzing Tim-3 expression with cancer progression, results revealed more elevated Tim-3 expression in CD3-CD56+ cells, CD3-$CD56^{dim}$ cells and CD3+CD56+ cells in cases with advanced stages (III/IV) than those with stage I and II (p=0.02, p=0.04 and p=0.01, respectively). In addition, Tim-3 expression was significantly reduced on after surgical resection of the primary tumor (p<0.01). Conclusions: Tim-3 expression in natural killer cells from fresh peripheral blood may provide a useful indicator of disease progression of lung cancer. Furthermore, it was indicated that Tim-3 might be as a therapeutic target.

키워드

참고문헌

  1. Anderson AC (2012). Tim-3, a negative regulator of anti-tumor immunity. Curr Opin Immunol, 24, 213-6. https://doi.org/10.1016/j.coi.2011.12.005
  2. Chiba S, Baghdadi M, Akiba H, et al (2012). Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat Immunol, 13, 832-42. https://doi.org/10.1038/ni.2376
  3. Da Silva IP, Gallois A, Jimenez-Baranda S, et al (2014). Reversal of NK- cell exhaustion in advanced melanoma by Tim-3 blockade. Cancer Immunol Res, 2, 410-22. https://doi.org/10.1158/2326-6066.CIR-13-0171
  4. Gleason MK, Lenvik TR, McCullar V, et al (2012). Tim-3 is an inducible human natural killer cell receptor that enhances interferon gamma production in response to galetin-9. Blood, 119, 3064-72. https://doi.org/10.1182/blood-2011-06-360321
  5. Gao X, Zhu Y, Li G, et al (2012). Tim-3 expression characterizes regulatoy T cells in tumor tissues and is associated with lung cancer progression. PloS One, 7, 30676. https://doi.org/10.1371/journal.pone.0030676
  6. Hasegawa H, Yamashita K, Otubo D, et al (2014). Allogeneic DCG promote lung NK cell activation and antitumor effect after invariant NKT cell activation. Anticancer Res, 34, 3411-7.
  7. Hodge G, Barnawi J, Jursevic, C, et al (2014). Lung cancer is associated with decreased expression of perforin, granzyme B and interferon (IFN)-$\gamma$ by infiltrating lung tissue T cells, natural killer (NK) T-like and NK cells. Clin Exp Immunol, 178, 79-85. https://doi.org/10.1111/cei.12392
  8. Ju Y, Hou N, Meng J, et al (2010). T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) mediates natural killer cell suppression in chronic hepatitis B. J Hepatol, 52, 322-9. https://doi.org/10.1016/j.jhep.2009.12.005
  9. Liu Y, Shu Q, Gao L, et al (2010). Increased Tim-3 xpression on peripheral lymphocytes from patients with rheumatoid arthritis negatively correlates with disease activity. Clin Immunol, 137, 288-95. https://doi.org/10.1016/j.clim.2010.07.012
  10. Liu YC, Zhou SB, Gao F, et al (2013). Chemotherapy and late course three dimensional conformal radiotherapy for treatment of patients with stage III non-small cell lung cancer. Asian Pac J Cancer Prev, 14, 2663-5. https://doi.org/10.7314/APJCP.2013.14.4.2663
  11. Lu YY, Huang XE, Xu L, et al (2013). Potential predictors of sensitivity to pemetrexed as first-line chemotherapy for patients with advanced non-squamous NSCLCs. Asian Pac J Cancer Prev, 14, 2005-8. https://doi.org/10.7314/APJCP.2013.14.3.2005
  12. Meggyes M, Miko E, Polgar B, et al (2014). Peripheral blood TIM-3 positive NK and CD8+ T cells throughout pregnancy: TIM-3/galectin-9 interaction and its possible role during pregnancy. PloS One, 9, 92371. https://doi.org/10.1371/journal.pone.0092371
  13. Ndhlovu LC, Lopez-Verges S, et al (2012). Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity. Blood, 119, 3734-43. https://doi.org/10.1182/blood-2011-11-392951
  14. Wang WJ, Tao Z, Gu W, et al (2013). Variation of blood T lymphocyte subgroups in patients with non-small cell lung cancer. Asian Pac J Cancer Prev, 14, 4671-3. https://doi.org/10.7314/APJCP.2013.14.8.4671
  15. Wu W, Shi Y, Li S, Zhang Y, et al (2012). Blockade of Tim-3 signaling restores the virus-specific CD8+ T cell response in patients with chronic hepatitis B. Eur J Immunol, 42, 1180-91. https://doi.org/10.1002/eji.201141852
  16. Yang X, Jiang X, Chen G, et al (2013). T cell Ig mucin-3 promotes homeostasis of sepsis by negatively regulating the TLR response. J Immunol, 190, 2068-79. https://doi.org/10.4049/jimmunol.1202661

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