Lung T-cell subset composition at the time of surgical resection is a prognostic indicator in non-small cell lung cancer
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NSCLC arises in the complex environment of chronic inflammation. Depending on lung immune polarization, infiltrating immune cells may either promote or suppress tumor growth. Despite the importance of the immune microenvironment, current staging techniques for NSCLC do not take into consideration the immune milieu in which the neoplasms arise. T-cell subset content was compared between paired tumor-bearing and contralateral lungs, patient and control peripheral blood. The relationship between T-cell subset distribution and survival were evaluated. CD4 and CD8+ T cells were subsetted by CD45RA/CD27 and analyzed for expression of activation, adhesion, and homing markers. Strikingly, T-cell content was indistinguishable between lungs. Compared with peripheral blood, naïve CD4 and CD8 T cells were rare in BAL. CD4+ BAL T cells showed increased CD95 (higher apoptotic potential) and CD103 expression (epithelial adhesion), but decreased CD38 (activation) and CCR7 expression (lymph node homing). CD8+ BAL T cells showed increased CD103 expression and decreased CD28 expression (co-stimulation). Differences in CD28, CD95, and CCR7 expression were more pronounced within memory cells, while differences in CD4+ CD103 expression were more prominent in effector/memory cells. Of these populations, the absence of lung CD4 T cells with an effector-like phenotype (CD45RA+/CD27−) emerged as a predictor of favorable outcome. Patients with a low proportion (≤0.44%) had 90% 5-year survival (n = 10, median survival 2,343 days), compared with 0% (n = 9, median survival 516 days) of patients with a higher proportion. Further study is required to confirm this association prospectively and define the function of this subpopulation.
KeywordsNon-small cell lung cancer Bronchoalveolar lavage T-cell subsets Biomarkers Prognosis
The authors would like to thank Drs. Theresa Whiteside and Jill Siegfried for their careful reading and critique of this manuscript. This work was supported by the Heart Lung and Esophageal Institute of the University of Pittsburgh Medical Center, and the University of Pittsburgh Lung Cancer SPORE: NCI P50-CA90440.
- 15.Donnenberg VS, Luketich JD, Landreneau RJ, Popovich AM, Donnenberg AD (2004) Influx and apoptosis of activated effector memory T cells in both lungs of patients with unilateral non-small cell lung cancer (NSCLC). In: Journal of clinical oncology, 2004 ASCO annual meeting proceedings, vol 22, no. 14S (July 15 Supplement), New Orleans, LA, p 7373Google Scholar
- 20.De Jong R, Brouwer M, Hooibrink B, van der Pouw-Kraan T, Miedema F, van Lier RAW (1992) The CD27− subset of peripheral blood memory CD4+ lymphocytes contains functionally differentiated T lymphocytes that develop by persistent antigenic stimulation in vivo. Eur J Immunol 22:993–999PubMedCrossRefGoogle Scholar
- 23.Heriberto P-G, Dolores A-C, Hector F-V, Juan Jose M, Jose Sullivan L-G (2005) Effector, memory and naive CD8+ T cells in peripheral blood and pleural effusion from lung adenocarcinoma patients. Lung Cancer (Amsterdam, Netherlands) 47:361–371Google Scholar
- 33.Rao NA (1997) Mechanisms of inflammatory response in sympathetic ophthalmia and VKH syndrome. Eye (Lond) 11(Pt 2):213–216Google Scholar
- 36.Rallón NI, López M, Soriano V, García-Samaniego J, Romero M, Labarga P, García-Gasco P, González-Lahoz J, Benito JM (2009) Level, phenotype and activation status of CD4+FoxP3+ regulatory T cells in patients chronically infected with human immunodeficiency virus and/or hepatitis C virus. Clin Exp Immunol 155:35–43PubMedCrossRefGoogle Scholar
- 39.Zhuang X, Xia X, Wang C, Gao F, Shan N, Zhang L, Zhang LA. High number of CD8+ T cells infiltrated in NSCLC Tissues is associated with a favorable prognosis. Appl Immunohistochem Mol Morphol 18:24–28Google Scholar