T Regulatory CD4+CD25+FoxP3+ Lymphocytes in the Peripheral Blood of Left-Sided Colorectal Cancer Patients
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. The Count of T Regulatory Lymphocytes in the Peripheral Blood of the Study Group
3.2. The Count of T Regulatory Lymphocytes in the Peripheral Blood of Cancer Patients vs. Control Group
3.3. The Impact of T Regulatory Lymphocytes Count in the Peripheral Blood on Survival
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
- Curiel, T.J.; Coukos, G.; Zou, L.; Alvarez, X.; Cheng, P.; Mottram, P.; Evdemon-Hogan, M.; Conejo-Garcia, J.R.; Zhang, L.; Burow, M.; et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med. 2004, 10, 942–949. [Google Scholar] [CrossRef] [PubMed]
- Zhou, Y.; Shao, N.; Aierken, N.; Xie, C.; Ye, R.; Qian, X.; Hu, Z.; Zhang, J.; Lin, Y. Prognostic value of tumor-infiltrating Foxp3+ regulatory T cells in patients with breast cancer: A meta-analysis. J. Cancer 2017, 8, 4098–4105. [Google Scholar] [CrossRef] [PubMed]
- Shen, Z.; Zhou, S.; Wang, Y.; Li, R.L.; Zhong, C.; Liang, C.; Sun, Y. Higher intratumoral infiltrated Foxp3+ Treg numbers and Foxp3+/CD8+ ratio are associated with adverse prognosis in resectable gastric cancer. J. Cancer Res. Clin. Oncol. 2010, 136, 1585–1595. [Google Scholar] [CrossRef] [PubMed]
- Gabitass, R.F.; Annels, N.E.; Stocken, D.D.; Pandha, H.A.; Middleton, G.W. Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13. Cancer Immunol. Immunother. 2011, 60, 1419–1430. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Seminerio, I.; Descamps, G.; Dupont, S.; de Marrez, L.; Laigle, J.A.; Lechien, J.R.; Kindt, N.; Journe, F.; Saussez, S. Infiltration of FoxP3+ Regulatory T Cells is a Strong and Independent Prognostic Factor in Head and Neck Squamous Cell Carcinoma. Cancers 2019, 11, 227. [Google Scholar] [CrossRef] [PubMed]
- Yoshioka, T.; Miyamoto, M.; Cho, Y.; Ishikawa, K.; Tsuchikawa, T.; Kadoya, M.; Li, L.; Mishra, R.; Ichinokawa, K.; Shoji, Y.; et al. Infiltrating regulatory T cell numbers is not a factor to predict patient’s survival in oesophageal squamous cell carcinoma. Br. J. Cancer 2008, 98, 1258–1263. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Kelaria, S.; Kerstetter, J.; Wang, J. The functional and prognostic implications of regulatory T cells in colorectal carcinoma. J. Gastrointest. Oncol. 2015, 6, 307–313. [Google Scholar] [CrossRef] [PubMed]
- Liyanage, U.K.; Moore, T.T.; Joo, H.-G.; Tanaka, Y.; Herrmann, V.; Doherty, G.; Drebin, J.A.; Strasberg, S.M.; Eberlein, T.J.; Goedegebuure, P.S.; et al. Prevalence of Regulatory T Cells Is Increased in Peripheral Blood and Tumor Microenvironment of Patients with Pancreas or Breast Adenocarcinoma. J. Immunol. 2002, 169, 2756–2761. [Google Scholar] [CrossRef] [PubMed]
- Szczepanik, A.M.; Siedlar, M.; Sierzega, M.; Goroszeniuk, D.; Bukowska-Strakova, K.; Czupryna, A.; Kulig, J. T-regulatory lymphocytes in peripheral blood of gastric and colorectal cancer patients. World J. Gastroenterol. 2011, 17, 343–348. [Google Scholar] [CrossRef] [PubMed]
- Liu, C.; Cheng, H.; Luo, G.; Lu, Y.; Jin, K.; Guo, M.; Ni, Q.; Yu, X. Circulating regulatory T cell subsets predict overall survival of patients with unresectable pancreatic cancer. Int. J. Oncol. 2017, 51, 686–694. [Google Scholar] [CrossRef]
- Napolitano, M.; D’Alterio, C.; Cardone, E.; Trotta, A.M.; Pecori, B.; Rega, D.; Pace, U.; Scala, D.; Scognamiglio, G.; Tatangelo, F. Peripheral myeloid-derived suppressor and T regulatory PD-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients. Oncotarget 2015, 6, 8261–8270. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Passardi, A.; Canale, M.; Valgiusti, M.; Ulivi, P. Immune Checkpoints as a Target for Colorectal Cancer Treatment. Int. J. Mol. Sci. 2017, 18, 1324. [Google Scholar] [CrossRef] [PubMed]
- Shitara, K.; Nishikawa, H. Regulatory T cells: A potential target in cancer immunotherapy. Ann. N Y Acad. Sci. 2018, 1417, 104–115. [Google Scholar] [CrossRef] [PubMed]
- Lim, D.R.; Kuk, J.K.; Kim, T.; Shin, E.J. Comparison of oncological outcomes of right-sided colon cancer versus left-sided colon cancer after curative resection: Which side is better outcome? Medicine 2017, 96, 42. [Google Scholar] [CrossRef]
- Benedix, F.; Kube, R.; Meyer, F.; Schmidt, U.; Gastinger, I.; Lippert, H. Comparison of 17,641 patients with right- and left-sided colon cancer: Differences in epidemiology, perioperative course, histology, and survival. Dis. Colon Rectum. 2010, 53, 57–64. [Google Scholar] [CrossRef] [PubMed]
- Derwinger, K.; Gustavsson, B. Variations in Demography and Prognosis by Colon Cancer Location. Anticancer Res. 2011, 31, 2347–2350. [Google Scholar] [PubMed]
- Shen, H.; Yang, J.; Huang, Q.; Jiang, M.J.; Tan, Y.N.; Fu, J.F.; Zhu, L.Z.; Fang, X.F.; Yuan, Y. Different treatment strategies and molecular features between right-sided and left-sided colon cancers. World J. Gastroenterol. 2015, 21, 6470–6478. [Google Scholar] [CrossRef] [PubMed]
- Curiel, T.J. Tregs and rethinking cancer immunotherapy. J. Clin Investig. 2007, 117, 1167–1174. [Google Scholar] [CrossRef]
- Takeuchi, Y.; Nishikawa, H. Roles of regulatory T cells in cancer immunity. Int Immunol. 2016, 28, 401–409. [Google Scholar] [CrossRef] [Green Version]
- Sellitto, A.; Galizia, G.; De Fanis, U.; Lieto, E.; Zamboli, A.; Orditura, M.; De Vita, F.; Giunta, R.; Lucivero, G.; Romano, C. Behavior of circulating CD4+CD25+Foxp3+ regulatory T cells in colon cancer patients undergoing surgery. J. Clin. Immunol. 2011, 31, 1095–1104. [Google Scholar] [CrossRef]
- Ling, K.L.; Pratap, S.E.; Bates, G.J.; Singh, B.; Mortensen, N.J.; George, B.D.; Warren, B.F.; Piris, J.; Roncador, G.; Fox, S.B.; et al. Increased frequency of regulatory T cells in peripheral blood and tumour infiltrating lymphocytes in colorectal cancer patients. Cancer Immun. 2007, 7, 7. [Google Scholar] [PubMed]
- Hua, W.; Yuan, A.; Zheng, W.; Li, C.; Cui, J.; Pang, Z.; Zhang, L.; Li, Z.; Goll, R.; Cui, G. Accumulation of FoxP3+ T regulatory cells in the tumor microenvironment of human colorectal adenomas. Pathol. Res. Pract. 2016, 212, 106–112. [Google Scholar] [CrossRef] [PubMed]
- Loddenkemper, C.; Schernus, M.; Noutsias, M.; Stein, H.; Thiel, E.; Nagorsen, D. In situ analysis of FOXP3+ regulatory T cells in human colorectal cancer. J. Transl. Med. 2006, 4, 52. [Google Scholar] [CrossRef] [PubMed]
- Liu, Z.; Huang, Q.; Liu, G.; Dang, L.; Chu, D.; Tao, K.; Wang, W. Presence of FOXP3(+)Treg cells is correlated with colorectal cancer progression. Int. J. Clin. Exp. Med. 2014, 7, 1781–1785. [Google Scholar] [PubMed]
- Betts, G.; Jones, E.; Junaid, S.; El-Shanawany, T.; Scurr, M.; Mizen, P.; Kumar, M.; Jones, S.; Rees, B.; Williams, G.; et al. Suppression of tumour-specific CD4+ T cells by regulatory T cells is associated with progression of human colorectal cancer. Gut 2012, 61, 1163–1171. [Google Scholar] [CrossRef] [PubMed]
- Kamarudin, A.N.; Cox, T.; Kolamunnage-Dona, R. Time-dependent ROC curve analysis in medical research: Current methods and applications. BMC Med. Res. Methodol. 2017, 17, 53. [Google Scholar] [CrossRef] [PubMed]
- Shang, B.; Liu, Y.; Jiang, S.-J.; Liu, Y. Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: A systematic review and meta-analysis. Sci. Rep. 2015, 5, 15179. [Google Scholar] [CrossRef] [PubMed]
Tumor Location | Number of Patients |
---|---|
Left colon | 43 |
Rectum | 51 |
T1 | 3 |
T2 | 15 |
T3 | 58 |
T4 | 18 |
N0 | 42 |
N1 | 28 |
N2 | 20 |
Nx | 4 |
M0 | 73 |
M1 | 21 |
Stage I | 15 |
Stage II | 28 |
Stage III | 30 |
Stage IV | 21 |
Grade 1 | 27 |
Grade 2 | 51 |
Grade 3 | 10 |
Grade not assessed | 6 |
R0 | 69 |
R1 | 3 |
R2 | 22 |
Group | Mean | Median | Min | Max | IQR |
---|---|---|---|---|---|
Study group | 10.35 | 6.0 | 1 | 123 | 7 |
Stage I | 14.46 | 9 | 1 | 52 | 8 |
Stage II | 6.82 | 5 | 1 | 123 | 7.5 |
Stage III | 8.9 | 6.5 | 1 | 37 | 6 |
Stage IV | 9.4 | 6 | 1 | 43 | 5 |
pN0 | 9.5 | 5.5 | 1 | 52 | 8 |
pN1 | 9.96 | 6 | 1 | 37 | 9 |
pN2 | 7.75 | 5.5 | 1 | 43 | 5.5 |
pT1 | 11.33 | 12 | 9 | 13 | 4 |
pT2 | 12.7 | 7 | 1 | 52 | 8 |
pT3 | 7.8 | 6 | 1 | 37 | 6 |
pT4 | 10.6 | 6.5 | 2 | 123 | 14 |
G1 | 8.5 | 5 | 1 | 45 | 8 |
G2 | 10.2 | 7 | 1 | 123 | 8 |
G3 | 7.7 | 5 | 1 | 21 | 7 |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Dylag-Trojanowska, K.; Rogala, J.; Pach, R.; Siedlar, M.; Baran, J.; Sierzega, M.; Zybaczynska, J.; Lenart, M.; Rutkowska-Zapala, M.; Szczepanik, A.M. T Regulatory CD4+CD25+FoxP3+ Lymphocytes in the Peripheral Blood of Left-Sided Colorectal Cancer Patients. Medicina 2019, 55, 307. https://doi.org/10.3390/medicina55060307
Dylag-Trojanowska K, Rogala J, Pach R, Siedlar M, Baran J, Sierzega M, Zybaczynska J, Lenart M, Rutkowska-Zapala M, Szczepanik AM. T Regulatory CD4+CD25+FoxP3+ Lymphocytes in the Peripheral Blood of Left-Sided Colorectal Cancer Patients. Medicina. 2019; 55(6):307. https://doi.org/10.3390/medicina55060307
Chicago/Turabian StyleDylag-Trojanowska, Katarzyna, Joanna Rogala, Radoslaw Pach, Maciej Siedlar, Jaroslaw Baran, Marek Sierzega, Justyna Zybaczynska, Marzena Lenart, Magdalena Rutkowska-Zapala, and Antoni M. Szczepanik. 2019. "T Regulatory CD4+CD25+FoxP3+ Lymphocytes in the Peripheral Blood of Left-Sided Colorectal Cancer Patients" Medicina 55, no. 6: 307. https://doi.org/10.3390/medicina55060307