The frequency of Th17 and Th22 cells in patients with colorectal cancer at pre-operation and post-operation

Ling, Limian; Zhao, Pingwei; Yan, Guoqiang; Chen, Mingxiao; Zhang, Ting; Wang, Lei; Jiang, Yanfang

doi:10.3109/08820139.2014.936445

Cited by 16 publications

(30 citation statements)

References 30 publications

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“…29 Another report showed that Th17 and Th22 cells were higher in CRC tissues and were negatively correlated with tumor progression. 31 The levels of IL22 and IL17 transcripts were also significantly higher in early stages of CRC, compared with advanced stages. 31 Interestingly, after tumor resection, their levels were significantly increased in patients with advanced stages.…”

Section: Discussionmentioning

confidence: 93%

Differential gene expression of tumor-infiltrating CD4 ⁺ T cells in advanced versus early stage colorectal cancer and identification of a gene signature of poor prognosis

et al. 2020

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Tumor-infiltrating lymphocytes (TILs) play indispensable roles in the progression and response to treatment of solid tumors. However, the prognostic significance of CD4 + TILs is not fully disclosed in cancers generally and in CRC in particular, mainly due to the existence of different functional subsets of CD4 + T cells. We performed transcriptomic profiling of CD4 + TILs isolated from CRC patients in order to identify differentially expressed genes and their functional pathways in early versus advanced disease stages. We found that in advanced stages, genes related to immune and inflammatory responses, in particular Th1mediated immune response and cytotoxicity-mediated genes, were downregulated; while epigeneticmediated silencing genes were upregulated. Interestingly, we identified genes, which were steadily upregulated or downregulated in CD4 + TILs with CRC progression from stage I to IV. Additionally, of the top 200 deregulated genes, 43 upregulated and 64 downregulated genes showed similar deregulation trends in the cancer genome atlas CRC dataset. From these 97 deregulated genes, we identified a "poor prognosis CD4 gene signature (ppCD4sig)". Patients with high ppCD4sig score showed shorter diseasespecific survival (DSS) and progression-free interval (PFI). The ppCD4sig was an independent prognostic indicator for DSS (HR = 1.73, 95% CI 1.32-2.27, P = 0.0001) and PFI (HR = 1.75, 95% CI 1.3-2.35, P = 0.0016). Additionally, patients at advanced stages and at a younger age (<55 years) were more likely to have a high ppCD4sig score. Altogether, our data provide novel insights and a unique prognostic gene signature of CD4 + TILs in the CRC microenvironment.

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Section: Discussionmentioning

confidence: 93%

Differential gene expression of tumor-infiltrating CD4 ⁺ T cells in advanced versus early stage colorectal cancer and identification of a gene signature of poor prognosis

et al. 2020

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“…In particular, CD45RO + memory T lymphocytes, cytotoxic CD8 + T cells (CTLs) and interferon (IFN)-γ-producing T helper1 cells (Th1) have been found to be associated with prolonged survival in CRC, irrespective of tumor stage ( 6 – 8 ), while the role of Th2 cells in colon cancer is mainly harmful as IL-4 directly and indirectly favors tumor growth ( 9 – 11 ). CD4 + T cells are now known to differentiate into additional effector T-cell subsets (i.e., Th17, Th9, follicular helper T, Th22) with contrasting and unclear roles in the development of CRC ( 12 – 14 ) as well as immunosuppressive cells, like exhausted, anergic/tolerant, and subsets of regulatory T cells (Tregs) that can favor cancer progression ( 15 – 18 ). In fact, the CD4 + CD25 + Foxp3 + Tregs subpopulation may exert a critical role in cancer promotion ( 19 , 20 ).…”

Section: Introductionmentioning

confidence: 99%

The Different Functional Distribution of “Not Effector” T Cells (Treg/Tnull) in Colorectal Cancer

et al. 2017

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Colorectal cancer (CRC) is the third most common cancer worldwide, ranking as high as the second leading cause of cancer-related deaths in industrialized countries. Consistent with immunosurveillance theory, the immune system is crucial to protect the host from developing tumors, and the major players in tumoral immunity are effector T cells. Anyway, cancer cells develop strategies of immunoevasion influencing the cancer-specific lymphocyte priming, activation, and effector function. Therefore, the T cell subsets that mature during the stages of tumor growth, differently contribute to disease progression and/or regression. In our study, we analyzed the intra-tumoral and peripheral T cell subsets’ distribution in 30 patients with CRC, in order to clarify their functional role toward cancer. We found that percentage of infiltrating effector T cells decreased in cancer tissue than in healthy mucosa and that the tumor microenvironment negatively influences the cytolytic activity of T lymphocytes reactive to cancer cells. Moreover, we found that the tumor tissue was infiltrated by a large amount of “not effector” T (neT) cells with a regulatory or an anergic profile, which are unable to kill cancer cells, may be contributing to the CRC promotion. The presence of neT cells was investigated also in the peripheral blood of CRC patients, demonstrating that the peripheral T regulatory cells can inhibit the proliferation of effector T cells, confirming their immunosuppressive properties. Finally, monitoring the changes in circulating neT cells’ frequencies after the tumor removal, we confirmed the role of cancer in the modulation of immune system, in particular, in supporting a Tregs-mediated immunosuppression.

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“…We and others have shown a higher frequency of IL-17-producing T cell populations, including MAIT cells and gd T cells, in tumor versus adjacent bowel tissue. [9][10][11][12][13][14] Differences in the frequency of regulatory T cells (Tregs) have also been observed, 10,11 but the effect of the function of these T cell populations on other infiltrating T cells is not clear. We hypothesized that T cells in tumor tissue would have impaired cytokine production and proliferative ability due to the suppressive environment in CRC tumors.…”

Section: Introductionmentioning

confidence: 99%

Functional impairment of infiltrating T cells in human colorectal cancer

et al. 2016

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T cells play a crucial role in preventing the growth and spread of colorectal cancer (CRC). However, immunotherapies against CRC have only shown limited success, which may be due to lack of understanding about the effect of the local tumor microenvironment (TME) on T cell function. The goal of this study was to determine whether T cells in tumor tissue were functionally impaired compared to T cells in non-tumor bowel (NTB) tissue from the same patients. We showed that T cell populations are affected differently by the TME. In the tumor, T cells produced more IL-17 and less IL-2 per cell than their counterparts from NTB tissue. T cells from tumor tissue also had impaired proliferative ability compared to T cells in NTB tissue. This impairment was not related to the frequency of IL-2 producing T cells or regulatory T cells, but T cells from the TME had a higher co-expression of inhibitory receptors than T cells from NTB. Overall, our data indicate that T cells in tumor tissue are functionally altered by the CRC TME, which is likely due to cell intrinsic factors. The TME is therefore an important consideration in predicting the effect of immune modulatory therapies.

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The frequency of Th17 and Th22 cells in patients with colorectal cancer at pre-operation and post-operation

Cited by 16 publications

References 30 publications

Differential gene expression of tumor-infiltrating CD4 ⁺ T cells in advanced versus early stage colorectal cancer and identification of a gene signature of poor prognosis

Differential gene expression of tumor-infiltrating CD4 ⁺ T cells in advanced versus early stage colorectal cancer and identification of a gene signature of poor prognosis

The Different Functional Distribution of “Not Effector” T Cells (Treg/Tnull) in Colorectal Cancer

Functional impairment of infiltrating T cells in human colorectal cancer

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The frequency of Th17 and Th22 cells in patients with colorectal cancer at pre-operation and post-operation

Cited by 16 publications

References 30 publications

Differential gene expression of tumor-infiltrating CD4 + T cells in advanced versus early stage colorectal cancer and identification of a gene signature of poor prognosis

Differential gene expression of tumor-infiltrating CD4 + T cells in advanced versus early stage colorectal cancer and identification of a gene signature of poor prognosis

The Different Functional Distribution of “Not Effector” T Cells (Treg/Tnull) in Colorectal Cancer

Functional impairment of infiltrating T cells in human colorectal cancer

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Differential gene expression of tumor-infiltrating CD4 ⁺ T cells in advanced versus early stage colorectal cancer and identification of a gene signature of poor prognosis

Differential gene expression of tumor-infiltrating CD4 ⁺ T cells in advanced versus early stage colorectal cancer and identification of a gene signature of poor prognosis