Correlation between Th17 cells and tumor microenvironment

doi:10.1016/j.cellimm.2013.06.001

Cellular Immunology

Volume 285, Issues 1–2, September–October 2013, Pages 18-22

https://doi.org/10.1016/j.cellimm.2013.06.001 Get rights and content

Highlights

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A development mechanism for Th17 cells in tumor microenvironment is proposed.
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Expression and migration of Th17 cells in tumor microenvironment.
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The balance between IL-17A and IL-17F in regulating tumor angiogenesis.
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The function of Th17 cells relies on the contradictory immune response to tumor.

Abstract

Since their identification in 2005, T helper (TH)17 cells have been proposed to play important roles in several human diseases, including various autoimmune conditions, inflammations, allergy, and tumors. Focusing on human studies, we review the current understanding of molecular interactions (IL-1β, IL-6, IL-23, IL-21 and TGF-β), the signaling pathway (STAT3 → RORγt) and the migration (induced by CCR6/CCL20) that contribute to Th17 differentiation and function in tumor microenvironment. Furthermore, we also make a synthesis of contradictory conclusions as to the roles that these cells are playing in the process of tumourigenesis in order to provide guidance of Th17-targeted therapy in tumors.

Introduction

Tumors develop in a complex and dynamic microenvironment. Surrounding or within the malignant tumor nests, stromal cells, endothelial cells, innate cells, and lymphocytes are present which interact with each other to form the tumor microenvironment. Studies have confirmed that the inflammatory context, the chemokine-orchestrated pattern of immune cells are considered to be important in tumor microenvironment. CD4⁺ T cells are essential organizers of cell-mediated immunity, participating in the each stage of immunity response. Uncommitted (naïve) CD4⁺ T cells can be induced to differentiate to specific lineages according to the local cytokine milieu, towards Th1, Th2, Th17 and Treg. [1] Furthermore, human Th17 cells release the proinflammatory cytokine IL-17. One important function of IL-17 seems to be coordination and regulation of local inflammation through up-regulation of other proinflammatory cytokines and chemokines [2]. Th17 cells play a potent proinflammatory role in certain infections, tumor and autoimmune disorders [3], which is a hot topic for researchers in recent years. Although advances about the discovery of Th17 cells have been made, the nature and role of Th17 cells in human tumor progression remain unknown. In this review, we will summarize the development, distribution, and function of Th17 cells in tumor microenvironment based on recent publications.

Section snippets

Cytokine-driven in Th17 cells development

The differentiation of naïve CD4⁺ T cells is controlled by many factors, such as the antigenicity, local cytokines and chemokines in tumor microenvironment. The balance and interaction of cytokines microenvironment during CD4⁺ T cells activation determine Th effector differentiation. Several studies demonstrated that the combination of IL-12 and IFN-γ can activate T-bet as a critical transcription factor for the differentiation of Th1 cells; IL-4 is important in competent polarization of Th2

The quantity change of Th17 cells in tumor microenvironment

Increased Th17 cells have been detected in both murine and human tumors. For instance, the increased proportion of Th17 cells can be found in rat models of maxillofacial neoplasm, fibrosarcoma, prostate carcinoma [20]. Th17 cells were also richer in peritumoral stroma of human HCC tissues than the normal liver tissues [21]. Consistently, compared with healthy volunteers, patients with gastric cancer had a higher proportion of Th17 cells in peripheral blood. Notably, the increased prevalence of

Th17 and angiogenesis

Th17 cells may play an important role in tumors, and Th17-related cytokines are inflammatory factors in mediating tumorigenesis and progression. Therefore, researchers make the function of Th17 cells in tumors as immediate areas of research focus.

Th17 cells are characterized as preferential producers of IL-17 which has six family members (IL-17A to IL-17F). IL-17A and IL-17F share the strongest amino acid homology, and their coding genes locate adjacent to each other on the chromosome [38]. The

Concluding remarks

The past several years have certified an outburst of information pertaining to the new lineage of CD4⁺ Th cells. IL-17-producing Th (Th17) cells, as a distinct lineage of CD4⁺ T helper cells, have not only changed the classical Th1/Th2 paradigm of Th cell differentiation but also markedly facilitated our understanding of human immunity. Although we deeply understand the mechanism of Th17 cells differentiation and regulation, the exact role of IL-17 in tumor immunopathogenesis remains undefined.

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ReviewCorrelation between Th17 cells and tumor microenvironment

Highlights

Abstract

Introduction

Section snippets

Cytokine-driven in Th17 cells development

The quantity change of Th17 cells in tumor microenvironment

Th17 and angiogenesis

Concluding remarks

Current Opinion in Immunology

Immunity

Trends in Immunology

Blood

Science Signalling

Cell

Biochemical and Biophysical Research Communications

Blood

Blood

Journal of Biological Chemistry

Journal of Hepatology

Blood

Blood

Blood

Are we ready to start studies of Th17 cell manipulation as a therapy for cancer?

Cancer Immunology Immunotherapy

A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17

Nature Immunology

Induction and effector functions of TH17 cells

Nature

IL-17 and Th17 cells

Annual Review of Immunology

Generation and differentiation of IL-17-producing CD4+ T cells in malignant pleural effusion

The Journal of Immunology

Generation of pathogenic TH17 cells in the absence of TGF-[bgr] signalling

Nature

Generation and regulation of human CD4+ IL-17-producing T cells in ovarian cancer

Proceedings of the National Academy of Sciences

The role and regulation of human Th17 cells in tumor immunity

The American Journal of Pathology

Future perspectives: should Th17 cells be considered as a possible therapeutic target in acute myeloid leukemia patients receiving allogeneic stem cell transplantation?

Cancer Immunology Immunotherapy

Review
Correlation between Th17 cells and tumor microenvironment

Generation and differentiation of IL-17-producing CD4⁺ T cells in malignant pleural effusion

Generation and regulation of human CD4⁺ IL-17-producing T cells in ovarian cancer