Impaired T cell function in malignant pleural effusion is caused by TGF‐β derived predominantly from macrophages. Issue 10 (6th August 2016)

• Record Type: Journal Article
• Authors: Li, Lifeng; Yang, Li; Wang, Liping; Wang, Fei; Zhang, Zhen; Li, Jieyao; Yue, Dongli; Chen, Xinfeng; Ping, Yu; Huang, Lan; Zhang, Bin; Zhang, Yi
• Is Part Of: International journal of cancer. Volume 139:Issue 10(2016:Nov. 15)
• Page Start: 2261
• Page End: 2269
• Publication Date: 2016-08-06
• Subjects: malignant pleural effusion (MPE) -- CD4+ T cells -- CD8+ T cells -- TGF‐β -- tumor‐associated macrophages (TAMs) -- impaired T cell function; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.30289
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Malignant pleural effusion (MPE) is an indication of advanced cancer. Immune dysfunction often occurs in MPE. We aimed to identify the reason for impaired T cell activity in MPE from lung cancer patients and to provide clues toward potential immune therapies for MPE. The surface inhibitory molecules and cytotoxic activity of T cells in MPE and peripheral blood (PB) were analyzed using flow cytometry. Levels of inflammatory cytokines in MPE and PB were tested using ELISA. TGF‐β expression in tumor‐associated macrophages (TAMs) was also analyzed. The effect of TAMs on T cells was verified in vitro . Lastly, changes in T cells were evaluated following treatment with anti‐TGF‐β antibody. We found that expression levels of Tim‐3, PD‐1 and CTLA‐4 in T cells from MPE were upregulated compared with those from PB, but levels of IFN‐γ and Granzyme B were downregulated ( p < 0.05). The amount of TGF‐β was significantly higher in MPE than in PB ( p < 0.05). TGF‐β was mainly produced by TAMs in MPE. When T cells were co‐cultured with TAMs, expression levels of Tim‐3, PD‐1 and CTLA‐4 were significantly higher than controls, whereas levels of IFN‐γ and Granzyme B were significantly decreased, in a dose‐dependent manner ( p < 0.05). In vitro treatment with anti‐TGF‐β antibody restored the impaired T cell cytotoxic activity in MPE. Our results indicate that macrophage‐derived TGF‐β plays an important role in impaired T cell cytotoxicity. It will therefore be valuable to develop therapeutic strategies against TGF‐β pathway for MPE therapy of lung cancer. Abstract : What's new? Malignant pleural effusion (MPE) often occurs in advanced lung cancer. Immune dysfunction is frequently seen in MPE, but the mechanisms are poorly understood. In this study, the authors found that T cells in MPE display a number of abnormalities, including an increase in inhibitory molecules and impaired cytotoxic activity. These appear to be related to an increase in TGF‐β production by tumor‐associated macrophages (TAMs). These results suggest that targeting the TGF‐β pathway could provide an effective therapeutic strategy for MPE.