The chemokine CXCL13 in lung cancers associated with environmental polycyclic aromatic hydrocarbons pollution

Abstract

More than 90% of lung cancers are caused by cigarette smoke and air pollution, with polycyclic aromatic hydrocarbons (PAHs) as key carcinogens. In Xuanwei City of Yunnan Province, the lung cancer incidence is among the highest in China, attributed to smoky coal combustion-generated PAH pollution. Here, we screened for abnormal inflammatory factors in non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used, and found that a chemokine CXCL13 was overexpressed in 63/70 (90%) of Xuanwei NSCLCs and 44/71 (62%) of smoker and 27/60 (45%) of non-smoker CR patients. CXCL13 overexpression was associated with the region Xuanwei and cigarette smoke. The key carcinogen benzo(a)pyrene (BaP) induced CXCL13 production in lung epithelial cells and in mice prior to development of detectable lung cancer. Deficiency in Cxcl13 or its receptor, Cxcr5, significantly attenuated BaP-induced lung cancer in mice, demonstrating CXCL13’s critical role in PAH-induced lung carcinogenesis.DOI: http://dx.doi.org/10.7554/eLife.09419.001

Tumor-infiltrating B cells: their role and application in anti-tumor immunity in lung cancer

“…16,17 Importantly, the B cell chemoattractant CXCL13, secreted by tumor cells, follicular dendritic cells, and T follicular helper cells in human lung tumor lesions, was shown to be responsible for the influx of B cells into the tumor. 16,18,19 Upon entering the local microenvironment, tumor antigens released from lung cancer cells aid in B cell aggregation and trigger B cellmediated antigen presentation, which facilitate the maintenance of B cell activation and proliferation. 19,20 Immunohistochemistry (IHC) and flow cytometric analysis show that all major subsets of B cells can be found within TIB populations (Table 1).…”

IL-4Rα-Expressing B Cells Are Required for CXCL13 Production by Fibroblastic Reticular Cells

“…In keeping with the previously reported role for CXCR5 + DCs in promoting the T helper 2 response development following Hp infection (Leó n et al, 2012), we found that the increase in CXCL13expressing cells located at the IFR correlated with increased accumulation of DCs in close association with ER-TR7 + fibers ( Figure S2E). The IFR is also known to be the site where antigen-activated B cells position themselves to receive T cell help (Garside et al, 1998;Wang et al, 2015). Thus, CXCL13 production by interfollicular MRC-like cells is likely to play an important role in the T cell-DC interactions that are known to be important in driving T helper 2 responses.…”

Effect of Polyaryl Hydrocarbons on Cytotoxicity in Monocytic Cells: Potential Role of Cytochromes P450 and Oxidative Stress Pathways

“…Tobacco-specific nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N’-nitrosonornicotine (NNN) are reported to cause lung cancer and oral cavity cancer [ 3 ]. PAHs are associated with several cancers such as skin, lung, oral, and breast cancer [ 4 – 7 ]. Among the hundreds of PAHs present in the cigarette smoke, benzo(a)pyrene (BaP) is the most extensively studied PAH due to its known carcinogenic effects.…”