Prognostic Significance of Tumor-infiltrating CD8⁺ or CD3⁺ T Lymphocytes and Interleukin-2 Expression in Radically Resected Non-small Cell Lung Cancer

Overview

Journal Chin Med J (Engl)

Specialty General Medicine

Date 2015 Jan 8

PMID 25563322

Citations 30

Authors

Chuntao Tian

Shixin Lu

Qingxia Fan

Weijie Zhang

Shunchang Jiao

Xiao Zhao

Zhiyong Wu

Liang Sun

Liuxing Wang

Affiliations

Soon will be listed here.

Abstract

Background: Altered immunoresponse is associated with tumorigenesis and cancer progression. This study assessed the levels of tumor-infiltrating CD3 + or CD8 + T lymphocytes and interleukin-2 (IL-2) protein in radically resected non-small cell lung cancer (NSCLC) tissues to predict overall survival (OS) of the patients.

Methods: Paraffin-embedded tissue specimens from 129 NSCLC patients were retrospectively collected for immunostaining of CD8 + , CD3 + , and IL-2 expression. Clinicopathological and survival data were collected and analyzed using the Chi-squared test, Kaplan-Meier curves, and the log-rank test or the Cox regression model.

Results: The data showed a significant inverse association between CD8 + T lymphocyte levels and IL-2 expression (r = -0.927; P = 0.000) and between the levels of CD8 + and CD3 + T lymphocytes (r = -0.722; P = 0.000), but a positive association between CD3 + T lymphocyte levels and IL-2 expression (r = 0.781; P = 0.000) in NSCLC tissues. Furthermore, the levels of CD3 + and CD8 + T lymphocytes and IL-2 expression were associated with tumor stage (P = 0.023, 0.006, and 0.031, respectively) and the level of CD8 + T lymphocytes was associated with the patient gender (P = 0.024). In addition, the levels of CD8 + T lymphocytes were associated with an unfavorable 5-year OS, whereas patients with high levels of CD3 + T lymphocytes in tumor lesions and IL-2-expressing tumors had significantly better 5-year OS rates than patients with low levels.

Conclusions: The levels of CD8 + T cells in tumor lesions and IL-2 expression were both independent predictors of OS for these NSCLC patients. Thus, the detection of tumor-infiltrating CD3 + or CD8 + T lymphocytes and IL-2 expression could be useful to predict the prognosis of radically resected NSCLC patients.

Citing Articles

Prognostic implications of tumor-infiltrating lymphocytes in non-small cell lung cancer: a systematic review and meta-analysis.

Yan Q, Li S, He L, Chen N Front Immunol. 2024; 15:1476365.

PMID: 39372398 PMC: 11449740. DOI: 10.3389/fimmu.2024.1476365.

Mechanisms of resistance to targeted therapy and immunotherapy in non-small cell lung cancer: promising strategies to overcoming challenges.

Xiang Y, Liu X, Wang Y, Zheng D, Meng Q, Jiang L Front Immunol. 2024; 15:1366260.

PMID: 38655260 PMC: 11035781. DOI: 10.3389/fimmu.2024.1366260.

Combined score of Y chromosome loss and T-cell infiltration improves UICC based stratification of esophageal adenocarcinoma.

Raters V, Gebauer F, Loser H, Schroder W, Schlosser H, Fuchs H Front Oncol. 2023; 13:1249172.

PMID: 38045001 PMC: 10693404. DOI: 10.3389/fonc.2023.1249172.

Tumoral Densities of T-Cells and Mast Cells Are Associated With Recurrence in Early-Stage Lung Adenocarcinoma.

Kammer M, Mori H, Rowe D, Chen S, Vasiukov G, Atwater T JTO Clin Res Rep. 2023; 4(9):100504.

PMID: 37674811 PMC: 10477685. DOI: 10.1016/j.jtocrr.2023.100504.

Tumor immune microenvironment (TIME) to enhance antitumor immunity.

Rajbhandary S, Dhakal H, Shrestha S Eur J Med Res. 2023; 28(1):169.

PMID: 37179365 PMC: 10182604. DOI: 10.1186/s40001-023-01125-3.

References

Kuo S, Chang D, Lee Y, Lee Y, Luh K . Tumour-infiltrating lymphocytes in non-small cell lung cancer are activated T lymphocytes. Respirology. 1998; 3(1):55-9. DOI: 10.1046/j.1440-1843.1998.d01-9.x. View

Dalgleish A, OByrne K . Inflammation and cancer: the role of the immune response and angiogenesis. Cancer Treat Res. 2006; 130:1-38. View

Kikuchi E, Yamazaki K, Torigoe T, Cho Y, Miyamoto M, Oizumi S . HLA class I antigen expression is associated with a favorable prognosis in early stage non-small cell lung cancer. Cancer Sci. 2007; 98(9):1424-30. PMC: 11159758. DOI: 10.1111/j.1349-7006.2007.00558.x. View

Groome P, Bolejack V, Crowley J, Kennedy C, Krasnik M, Sobin L . The IASLC Lung Cancer Staging Project: validation of the proposals for revision of the T, N, and M descriptors and consequent stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol. 2007; 2(8):694-705. DOI: 10.1097/JTO.0b013e31812d05d5. View

Yie S, Yang H, Ye S, Li K, Dong D, Lin X . Expression of human leucocyte antigen G (HLA-G) is associated with prognosis in non-small cell lung cancer. Lung Cancer. 2007; 58(2):267-74. DOI: 10.1016/j.lungcan.2007.06.011. View

Kasprzak A, Olejniczak K, Przybyszewska W, Zabel M . Cellular expression of interleukin 2 (IL-2) and its receptor (IL-2R, CD25) in lung tumours. Folia Morphol (Warsz). 2007; 66(3):159-66. View

Mantovani A, Allavena P, Sica A, Balkwill F . Cancer-related inflammation. Nature. 2008; 454(7203):436-44. DOI: 10.1038/nature07205. View

Kawai O, Ishii G, Kubota K, Murata Y, Naito Y, Mizuno T . Predominant infiltration of macrophages and CD8(+) T Cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer. Cancer. 2008; 113(6):1387-95. DOI: 10.1002/cncr.23712. View

Ruffini E, Asioli S, Filosso P, Lyberis P, Bruna M, Macri L . Clinical significance of tumor-infiltrating lymphocytes in lung neoplasms. Ann Thorac Surg. 2009; 87(2):365-71. DOI: 10.1016/j.athoracsur.2008.10.067. View

10.

Karagoz B, Bilgi O, Gumus M, Akyol Erikci A, Sayan O, Turken O . CD8+CD28- cells and CD4+CD25+ regulatory T cells in the peripheral blood of advanced stage lung cancer patients. Med Oncol. 2009; 27(1):29-33. DOI: 10.1007/s12032-008-9165-9. View

11.

Al-Shibli K, Al-Saad S, Andersen S, Donnem T, Bremnes R, Busund L . The prognostic value of intraepithelial and stromal CD3-, CD117- and CD138-positive cells in non-small cell lung carcinoma. APMIS. 2010; 118(5):371-82. DOI: 10.1111/j.1600-0463.2010.02609.x. View

12.

Jemal A, Siegel R, Xu J, Ward E . Cancer statistics, 2010. CA Cancer J Clin. 2010; 60(5):277-300. DOI: 10.3322/caac.20073. View

13.

Hwang W, Adams S, Tahirovic E, Hagemann I, Coukos G . Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis. Gynecol Oncol. 2011; 124(2):192-8. PMC: 3298445. DOI: 10.1016/j.ygyno.2011.09.039. View

14.

Soini Y, Paakko P . High number of tumour-infiltrating lymphocytes is associated with apoptosis in non-small cell lung carcinoma. APMIS. 2001; 109(7-8):525-32. View

15.

Ortegel J, Staren E, Faber L, Warren W, Braun D . Modulation of tumor-infiltrating lymphocyte cytolytic activity against human non-small cell lung cancer. Lung Cancer. 2002; 36(1):17-25. DOI: 10.1016/s0169-5002(01)00472-x. View

16.

Neuner A, Schindel M, Wildenberg U, Muley T, Lahm H, Fischer J . Prognostic significance of cytokine modulation in non-small cell lung cancer. Int J Cancer. 2002; 101(3):287-92. DOI: 10.1002/ijc.10604. View

17.

Dunn G, Bruce A, Ikeda H, Old L, Schreiber R . Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002; 3(11):991-8. DOI: 10.1038/ni1102-991. View

18.

Kataki A, Scheid P, Piet M, Marie B, Martinet N, Martinet Y . Tumor infiltrating lymphocytes and macrophages have a potential dual role in lung cancer by supporting both host-defense and tumor progression. J Lab Clin Med. 2002; 140(5):320-8. DOI: 10.1067/mlc.2002.128317. View

19.

Wakabayashi O, Yamazaki K, Oizumi S, Hommura F, Kinoshita I, Ogura S . CD4+ T cells in cancer stroma, not CD8+ T cells in cancer cell nests, are associated with favorable prognosis in human non-small cell lung cancers. Cancer Sci. 2003; 94(11):1003-9. PMC: 11160236. DOI: 10.1111/j.1349-7006.2003.tb01392.x. View

20.

Trojan A, Urosevic M, Dummer R, Giger R, Weder W, Stahel R . Immune activation status of CD8+ T cells infiltrating non-small cell lung cancer. Lung Cancer. 2004; 44(2):143-7. DOI: 10.1016/j.lungcan.2003.11.004. View