Abstract
The role of tumor-infiltrating T cell subsets in the prognosis of non-Hodgkin’s lymphoma (NHL) has previously been reported. In the present study, we investigated the prognostic significance of different T cell subsets in the peripheral blood of NHL patients. Immunophenotyping was performed on the peripheral blood samples of 45 patients with newly diagnosed B cell NHL using flow cytometry. The relationship between T cell subsets of CD4+, CD8+, CD3+CD25+, CD4+CD25+, CD4+CD25high [as T regulatory cells (T reg)], and the CD4/CD8 ratio with international prognostic index (IPI) and response to therapy was determined. The percentages of CD3+, CD4+, and CD8+ T cells in the peripheral blood of the patients were 49.1 ± 20.3%, 23.6 ± 11%, and 31.4 ± 14.4%, respectively (CD4/CD8 ratio: 0.92 ± 0.6). There were 4.2 ± 3.2% T reg cells. A study of the percentage of T cells in relation to IPI score showed a higher proportion of CD3+CD25+, CD4+, and CD4+CD25+ cells in low-risk patients compared with intermediate/high risk groups (p < 0.05). The above cells, as well as CD4+CD25high T reg cells, indicated a positive correlation with complete remission (CR) and survival. CD4 positivity correlated significantly with survival and CR durations, which were longer in patients with ≥20% CD4+ cells than those with <20% CD4+ cells, thus indicating the prognostic value of CD4+ T cells in NHL patients. There was no significant data on CD8+ cells as well as the CD4/CD8 ratio between distinct IPI groups and response to therapy. These data indicated the importance of CD4+ cells and the activation status of T cells in immunity against lymphoma and the prognostic implication of enumeration of these cells in NHL patients.
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References
Lichtman MA, Beutler E, Kipps TJ, et al. Williams text book of hematology.7th ed. New York, NY: Mc Graw Hill; 2006.
Betts GJ, Clarke SL, Richards HE, et al. Regulating the immune response to tumors. Adv Drug Deliv Rev. 2006;58:948–61.
Grulich AE, Vajdic CM, Cozen W. Altered immunity as a risk factor for non-Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev. 2007;16:405–8.
Vasei M, Kumar PV, Malekhosseini SA, Amirghofran Z. Primary T-cell lymphoma of the breast with lymphoepithelial lesion. A case report. APMIS. 1997;105:445–8.
Nogai H, Dörken B, Lenz G. Pathogenesis of Non-Hodgkin’s lymphoma. J Clin Oncol. 2011;29:1803–11.
Sznurkowski JJ, Zawrocki A, Emerich J, et al. Prognostic significance of CD4+ and CD8+ T cell infiltration within cancer cell nests in vulvar squamous cell carcinoma. Int J Gynecol Cancer. 2011;21:717–21.
Waldner M, Schimanski CC, Neurath MF. Colon cancer and the immune system: the role of tumor invading T cells. World J Gastroenterol. 2006;12:7233–8.
Ansell SM, Stenson M, Habermann TM, et al. CD4+ T-cell immune response to large B-cell non-Hodgkin’s lymphoma predicts patient outcome. J Clin Oncol. 2001;19:720–6.
Wansom D, Light E, Worden F, et al. Correlation of cellular immunity with human papillomavirus status and outcome in patients with advanced oropharyngeal cancer. Arch Otolaryngol Head Neck Surg. 2010;136:1267–73.
Hernberg MM, Hahka-Kemppinen MH, Pyrhonen SO. The prognostic role of CD4+ and CD8+ lymphocytes during chemoimmunotherapy in metastatic melanoma. Melanoma Res. 2004;14:493–500.
Gorczyca W, Weisberger J, Liu Z, et al. An approach to diagnosis of T-cell lymphoproliferative disorders by flow cytometry. Cytometry. 2002;50:177–90.
Medeiros LJ, Harmon DC, Linggood RM, et al. Immunohistologic features predict clinical behavior of orbital and conjunctival lymphoid infiltrates. Blood. 1989;74:2121–9.
Slymen DJ, Miller TP, Lippman SM, et al. Immunobiologic factors predictive of clinical outcome in diffuse large-cell lymphoma. J Clin Oncol. 1990;8:986–93.
Mougiakakos D, Choudhury A, Lladser A, et al. Regulatory Tcells in cancer. Adv Cancer Res. 2010;107:57–117.
Feng LL, Wang X. Targeting Foxp3+ regulatory T cells-related immunosuppression for cancer immunotherapy. Chin Med J (Engl). 2010;123:3334–42.
Yang ZZ, Novak AJ, Ziesmer SC, et al. Attenuation of CD8+ T-cell function by CD4+CD25+ regulatory T cells in B-cell non-Hodgkin’s lymphoma. Cancer Res. 2006;66:10145–52.
Brusko TM, Wasserfall CH, Clare-Salzler MJ, et al. Functional defects and the influence of age on the frequency of CD4+CD25+ T-cells in type 1 diabetes. Diabetes. 2005;54:1407–14.
Ziepert M, Hasenclever D, Kuhnt E, et al. Standard International prognostic index remains a valid predictor of outcome for patients with aggressive CD20+ B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28:2373–80.
Kapplan EL, Meier P. Non-parametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.
Shahghasempour SH, Gerami M, Entezami Z. Enumeration of peripheral blood lymphocyte subsets in a healthy Iranian population. Arch Iran Med. 2001;4:80–3.
Beyer M, Schultze JL. Regulatory T cells in cancer. Blood. 2006;108:804–8.
Chatzitolios A, Venizelos I, Tripsiannis G, et al. Prognostic significance of CD95, P53, and BCL2 expression in extranodal non-Hodgkin’s lymphoma. Ann Hematol. 2010;89:889–96.
Váróczy L, Gergely L, Miltényi Z, et al. Can CD3+/HLA-DR+ activated T cells predict the prognosis of non-Hodgkin’s lymphoma patients? Immunol Lett. 2005;97:155–7.
Xu Y, Kroft SH, McKenna RW, et al. Prognostic significance of tumour-infiltrating T lymphocytes and T-cell subsets in de novo diffuse large B-cell lymphoma: a multiparameter flow cytometry study. Br J Haematol. 2001;112:945–9.
Liu L, Yao J, Ding Q, et al. CD4+CD25 high regulatory cells in peripheral blood of NSCLC patients. J Huazhong Univ Sci Technol Med Sci. 2006;26:548–51.
Marshall NA, Culligan DJ, Tighe J, et al. The relationships between Epstein-Barr virus latent membrane protein 1 and regulatory T cells in Hodgkin’s lymphoma. Exp Hematol. 2007;35:596–604.
Alvaro T, Lejeune M, Salvadó MT, et al. Immunohistochemical patterns of reactive microenvironment are associated with clinicobiologic behavior in follicular lymphoma patients. J Clin Oncol. 2006;24:5350–7.
Shi X, Zhang XS, Liu DG, et al. CD4+CD25+ T regulatory cells in peripheral blood of B-NHL patients with or without chemotherapy. Ai Zheng. 2004;23:597–601.
Tzankov A, Meier C, Hirschmann P, et al. Correlation of high numbers of intratumoral FOXP3+ regulatory T cells with improved survival in germinal center-like diffuse large B-cell lymphoma, follicular lymphoma and classical Hodgkin’s lymphoma. Haematologica. 2008;93:193–200.
Coupland SE. The challenge of the microenvironment in B-cell lymphomas. Histopathology. 2011;58:69–80.
Montserrat E, Campo E, Banham AH, et al. High numbers of tumor-infiltrating FOXP3-positive regulatory T cells are associated with improved overall survival in follicular lymphoma. Blood. 2006;108:2957–64.
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This work was supported by grant no 3554 from Shiraz University of Medical Sciences.
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Dehghani, M., Sharifpour, S., Amirghofran, Z. et al. Prognostic significance of T cell subsets in peripheral blood of B cell non-Hodgkin’s lymphoma patients. Med Oncol 29, 2364–2371 (2012). https://doi.org/10.1007/s12032-012-0176-1
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DOI: https://doi.org/10.1007/s12032-012-0176-1