• Anti-CTLA-4
• Anti-PD1
• ICI
• Th subsets
• Tumor immunity

• Humans
• Immune Checkpoint Inhibitors/therapeutic use
• Immune Checkpoint Inhibitors/pharmacology
• Neoplasms/immunology
• Neoplasms/drug therapy
• Tumor Microenvironment/immunology
• Tumor Microenvironment/drug effects
• Animals
• T-Lymphocytes, Helper-Inducer/immunology
• T-Lymphocytes, Helper-Inducer/drug effects
• T-Lymphocyte Subsets/immunology

• chemokine
• chemokine receptor
• esophageal carcinoma
• immunosuppression
• tumor microenvironment

• CCL22
• CCL25
• acute myeloid leukemia (AML)
• bone marrow
• chemokine
• leukemia
• myelodysplastic neoplasms (MDS)

• Chemokine
• Chemokine receptor
• Esophageal cancer
• Therapeutic potential
• Tumor microenvironment

• Humans
• Esophageal Neoplasms/metabolism
• Esophageal Neoplasms/therapy
• Esophageal Neoplasms/pathology
• Esophageal Neoplasms/immunology
• Tumor Microenvironment
• Chemokines/metabolism
• Receptors, Chemokine/metabolism
• Biomarkers, Tumor/metabolism
• Prognosis

• (2022TSYCLJ0031) Leading talent project of scientific and technological innovation in Tianshan talents training plan of Xinjiang Uygur Autonomous Region
• (SKL-HIDCA-2022-14, SKL-HIDCA-2020-JZ2 Project from State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia
• 2022D01D69 Natural Science Foundation of Xinjiang
• 2020B03003-1 Key Research and Development Project of the Xinjiang Uygur Autonomous Region
• (82260568) The study was partly supported by Natural Science Foundation of China

• IL-17
• PsA
• neutrophils
• psoriasis
• secukinumab

• Humans
• Arthritis, Psoriatic/drug therapy
• Arthritis, Psoriatic/chemically induced
• Neutrophils
• Interleukin-17
• Antibodies, Monoclonal/therapeutic use
• Psoriasis/drug therapy
• Treatment Outcome

• 21430 Versus Arthritis
• MR/P020941/1 Medical Research Council

• esophageal squamous cell cancer
• immune evasion
• immunosuppression
• immunotherapy
• tumor microenvironment

• National Key Research and Development Program of China
• National Natural Science Foundation of China
• China Postdoctoral Science Foundation
• Natural Science Foundation of Shandong Province

• Humans
• Th17 Cells
• Quality of Life
• Autoimmune Diseases
• T-Lymphocytes, Regulatory
• Inflammation
• Cytokines/metabolism

• monoclonal antibody
• mouse CCR6
• peptide immunization

Various immune cells are involved in host immune responses to cancer. T-helper (Th) 1 cells, cytotoxic CD8⁺ T cells, and natural killer cells are the major effector cells in anti-tumor immunity, whereas cells such as regulatory T cells and myeloid-derived suppressor cells are negatively involved in anti-tumor immunity. Th2 cells and Th17 cells have been shown to have both pro-tumor and anti-tumor activities. The migratory properties of various immune cells are essential for their function and critically regulated by the chemokine superfamily. In this review, we summarize the roles of various immune cells in tumor immunity and their migratory regulation by the chemokine superfamily. We also assess the therapeutic possibilities of targeting chemokines and chemokine receptors in cancer immunotherapy.

Various immune cells are involved in host tumor immune responses. In particular, there are many T cell subsets with different roles in tumor immunity. T-helper (Th) 1 cells are involved in cellular immunity and thus play the major role in host anti-tumor immunity by inducing and activating cytotoxic T lymphocytes (CTLs). On the other hand, Th2 cells are involved in humoral immunity and suppressive to Th1 responses. Regulatory T (Treg) cells negatively regulate immune responses and contribute to immune evasion of tumor cells. Th17 cells are involved in inflammatory responses and may play a role in tumor progression. However, recent studies have also shown that Th17 cells are capable of directly inducting CTLs and thus may promote anti-tumor immunity. Besides these T cell subsets, there are many other innate immune cells such as dendritic cells (DCs), natural killer (NK) cells, and myeloid-derived suppressor cells (MDSCs) that are involved in host immune responses to cancer. The migratory properties of various immune cells are critical for their functions and largely regulated by the chemokine superfamily. Thus, chemokines and chemokine receptors play vital roles in the orchestration of host immune responses to cancer. In this review, we overview the various immune cells involved in host responses to cancer and their migratory properties regulated by the chemokine superfamily. Understanding the roles of chemokines and chemokine receptors in host immune responses to cancer may provide new therapeutic opportunities for cancer immunotherapy.

• Th1
• Th17
• Th2
• chemokine
• chemokine receptor
• dendritic cell
• macrophage
• neutrophil
• regulatory T
• tumor microenvironment

• Cancer
• Immune response
• Interleukin-17
• Pathophysiology
• Th17 cells
• Tumor microenvironment

• ILC1s
• Th17
• bladder cancer
• clustering
• innate lymphoid cells

• Aged
• Antigens, CD/metabolism
• Antigens, Differentiation, T-Lymphocyte/metabolism
• Cell Differentiation
• Female
• Flow Cytometry
• Hepatitis A Virus Cellular Receptor 2/metabolism
• Humans
• Image Cytometry
• Immunity, Cellular
• Interferon-gamma/metabolism
• Interleukin-17/metabolism
• Interleukins/metabolism
• Lectins, C-Type/metabolism
• Lymphocytes, Tumor-Infiltrating/cytology
• Lymphocytes, Tumor-Infiltrating/immunology
• Lymphocytes, Tumor-Infiltrating/metabolism
• Male
• Natural Cytotoxicity Triggering Receptor 1/metabolism
• Natural Cytotoxicity Triggering Receptor 3/metabolism
• Neoplasm Invasiveness
• Perforin/metabolism
• Programmed Cell Death 1 Receptor/metabolism
• Th17 Cells/cytology
• Th17 Cells/immunology
• Th17 Cells/metabolism
• Urinary Bladder Neoplasms/immunology
• Urinary Bladder Neoplasms/pathology
• Interleukin-22

• Glenda and Gary Woods Distinguished Chair in GU Oncology
• RP170345 Cancer Prevention and Research Institute of Texas
• T32 GM113896 NIGMS NIH HHS
• RP150600 BASiC core
• Bladder Cancer Advocacy Network (BCAN)
• P30 CA054174 NCI NIH HHS
• Roger L. And Laura D. Zeller Charitable Foundation Chair in Urologic Cancer
• CDMRP CA170270/P1P2
• Max & Minnie Tomerlin Voelcker Fund
• Cancer Prevention and Research Institute of Texas
• Max & Minnie Tomerlin Voelcker Fund

• Chemokine receptor antagonist
• Combination treatment
• Immunotherapy
• Tumour immunology
• Tumour microenvironment

The immune response against cancer is generated by effector T cells, among them cytotoxic CD8⁺ T cells that destroy cancer cells and helper CD4⁺ T cells that mediate and support the immune response. This antitumor function of T cells is tightly regulated by a particular subset of CD4⁺ T cells, named regulatory T cells (Tregs), through different mechanisms. Even if the complete inhibition of Tregs would be extremely harmful due to their tolerogenic role in impeding autoimmune diseases in the periphery, the targeted blockade of their accumulation at tumor sites or their targeted depletion represent a major therapeutic challenge. This review focuses on the mechanisms favoring Treg recruitment, expansion and stabilization in the tumor microenvironment and the therapeutic strategies developed to block these mechanisms.

Regulatory T cells (Tregs) are present in a large majority of solid tumors and are mainly associated with a poor prognosis, as their major function is to inhibit the antitumor immune response contributing to immunosuppression. In this review, we will investigate the mechanisms involved in the recruitment, amplification and stability of Tregs in the tumor microenvironment (TME). We will also review the strategies currently developed to inhibit Tregs’ deleterious impact in the TME by either inhibiting their recruitment, blocking their expansion, favoring their plastic transformation into other CD4⁺ T-cell subsets, blocking their suppressive function or depleting them specifically in the TME to avoid severe deleterious effects associated with Treg neutralization/depletion in the periphery and normal tissues.

• proliferation
• recruitment
• regulatory T cells
• stability
• therapeutic targeting
• tumor microenvironment

• dendritic cells
• inflammation
• radiotherapy
• rectal cancer
• tumour immunology

• GOIPG/2017/983 Irish Research Council

CC chemokines, a subfamily of 27 chemotactic cytokines, are a component of intercellular communication, which is crucial for the functioning of the tumor microenvironment. Although many individual chemokines have been well researched, there has been no comprehensive review presenting the role of all known human CC chemokines in the hallmarks of cancer, and this paper aims at filling this gap. The first part of this review discusses the importance of CCL1, CCL3, CCL4, CCL5, CCL18, CCL19, CCL20, CCL21, CCL25, CCL27, and CCL28 in cancer. Here, we discuss the significance of CCL2 (MCP-1), CCL7, CCL8, CCL11, CCL13, CCL14, CCL15, CCL16, CCL17, CCL22, CCL23, CCL24, and CCL26. The presentation of each chemokine includes its physiological function and then the role in tumor, including proliferation, drug resistance, migration, invasion, and organ-specific metastasis of tumor cells, as well as the effects on angiogenesis and lymphangiogenesis. We also discuss the effects of each CC chemokine on the recruitment of cancer-associated cells to the tumor niche (eosinophils, myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM), tumor-associated neutrophils (TAN), regulatory T cells (T_reg)). On the other hand, we also present the anti-cancer properties of CC chemokines, consisting in the recruitment of tumor-infiltrating lymphocytes (TIL).

• CC chemokine
• MCP-1
• angiogenesis
• anti-cancer therapy
• cancer
• chemokine
• lymphangiogenesis
• organ-specific metastasis
• tumor
• tumor microenvironment

CC chemokines (or β-chemokines) are 28 chemotactic cytokines with an N-terminal CC domain that play an important role in immune system cells, such as CD4⁺ and CD8⁺ lymphocytes, dendritic cells, eosinophils, macrophages, monocytes, and NK cells, as well in neoplasia. In this review, we discuss human CC motif chemokine ligands: CCL1, CCL3, CCL4, CCL5, CCL18, CCL19, CCL20, CCL21, CCL25, CCL27, and CCL28 (CC motif chemokine receptor CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 ligands). We present their functioning in human physiology and in neoplasia, including their role in the proliferation, apoptosis resistance, drug resistance, migration, and invasion of cancer cells. We discuss the significance of chemokine receptors in organ-specific metastasis, as well as the influence of each chemokine on the recruitment of various cells to the tumor niche, such as cancer-associated fibroblasts (CAF), Kupffer cells, myeloid-derived suppressor cells (MDSC), osteoclasts, tumor-associated macrophages (TAM), tumor-infiltrating lymphocytes (TIL), and regulatory T cells (T_reg). Finally, we show how the effect of the chemokines on vascular endothelial cells and lymphatic endothelial cells leads to angiogenesis and lymphangiogenesis.

• CC chemokine
• angiogenesis
• cancer
• chemokine
• lymphangiogenesis
• organ-specific metastasis
• tumor
• tumor microenvironment

• Animals
• Cell Proliferation
• Chemokines, CC/metabolism
• Humans
• Neoplasms/metabolism
• Neoplasms/pathology
• Receptors, CCR/metabolism
• Signal Transduction
• Tumor Microenvironment

Hypoxia, i.e., oxygen deficiency condition, is one of the most important factors promoting the growth of tumors. Since its effect on the chemokine system is crucial in understanding the changes in the recruitment of cells to a tumor niche, in this review we have gathered all the available data about the impact of hypoxia on β chemokines. In the introduction, we present the chronic (continuous, non-interrupted) and cycling (intermittent, transient) hypoxia together with the mechanisms of activation of hypoxia inducible factors (HIF-1 and HIF-2) and NF-κB. Then we describe the effect of hypoxia on the expression of chemokines with the CC motif: CCL1, CCL2, CCL3, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL15, CCL16, CCL17, CCL18, CCL19, CCL20, CCL21, CCL22, CCL24, CCL25, CCL26, CCL27, CCL28 together with CC chemokine receptors: CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10. To better understand the effect of hypoxia on neoplastic processes and changes in the expression of the described proteins, we summarize the available data in a table which shows the effect of individual chemokines on angiogenesis, lymphangiogenesis, and recruitment of eosinophils, myeloid-derived suppressor cells (MDSC), regulatory T cells (T_reg), and tumor-associated macrophages (TAM) to a tumor niche.

• NF-κB
• cancer
• chemokine
• hypoxia
• hypoxia inducible factor

• Chemokines/metabolism
• Humans
• Neoplasms/metabolism
• Receptors, CCR/metabolism
• Signal Transduction
• Tumor Hypoxia
• Tumor Microenvironment

• CCL20-CCR6 axis
• cancer progression
• chemokines

• Cell Movement/immunology
• Cell Proliferation
• Chemokine CCL20/metabolism
• Chemokines/metabolism
• Disease Progression
• Humans
• Macrophages/immunology
• Neoplasms/immunology
• Neoplasms/metabolism
• Receptors, CCR6/metabolism
• T-Lymphocytes, Helper-Inducer/immunology
• T-Lymphocytes, Regulatory/immunology
• Tumor Microenvironment/immunology

Esophageal cancer (EC) is the sixth most deadly cancer, and its incidence is still increasing year by year. Although the researches on the molecular mechanisms of EC have been widely carried out and incremental progress has been made, its overall survival rate is still low. There is cumulative evidence showing that the esophageal microenvironment plays a vital role in the development of EC. In precancerous lesions of the esophagus, high-risk environmental factors can promote the development of precancerous lesions by inducing the production of inflammatory factors and the recruitment of immune cells. In the tumor microenvironment, tumor-promoting cells can inhibit anti-tumor immunity and promote tumor progression through a variety of pathways, such as bone marrow-derived suppressor cells (MDSCs), tumor-associated fibroblasts (CAFs), and regulatory T cells (Tregs). The formation of extracellular hypoxia and acidic microenvironment and the change of extracellular matrix stiffness are also important factors affecting tumor progression and metastasis. Simultaneously, primary tumor-derived cytokines and bone marrow-derived immune cells can also promote the formation of pre-metastasis niche of EC lymph nodes, which are beneficial to EC lymph node metastasis. Further research on the specific mechanism of these processes in the occurrence, development, and metastasis of each EC subtype will support us to grasp the overall pre-cancerous prevention, targeted treatment, and metastatic assessment of EC.

• esophageal cancer
• premetastatic niche
• tumor microenvironment
• tumor precursor microenvironment

Th17 cells represent a subset of CD4+ T cells characterized by the master transcription factor RORγt and the production of IL-17. Epigenetic modifications such as post-translational histone modifications and DNA methylation play a key role in Th17 cell differentiation and high plasticity. Th17 cells are highly recruited in many types of cancer and can be associated with good or bad prognosis. Here, we will review the remodeling of the epigenome induced by the tumor microenvironment, which may explain Th17 cell predominance. We will also discuss the promising treatment perspectives of molecules targeting epigenetic enzymes to remodel a Th17-enriched tumor microenvironment.

• TIL
• Th17 cells
• epigenetic modifications
• tumor microenvironment

IL-17 is produced by RAR-related orphan receptor gamma t (RORγt)-expressing cells including Th17 cells, subsets of γδT cells and innate lymphoid cells (ILCs). The biological significance of IL-17-producing cells is well-studied in contexts of inflammation, autoimmunity and host defense against infection. While most of available studies in tumor immunity mainly focused on the role of T-bet-expressing cells, including cytotoxic CD8⁺ T cells and NK cells, and their exhaustion status, the role of IL-17-producing cells remains poorly understood. While IL-17-producing T-cells were shown to be anti-tumorigenic in adoptive T-cell therapy settings, mice deficient in type 17 genes suggest a protumorigenic potential of IL-17-producing cells. This review discusses the features of IL-17-producing cells, of both lymphocytic and myeloid origins, as well as their suggested pro- and/or anti-tumorigenic functions in an organ-dependent context. Potential therapeutic approaches targeting these cells in the tumor microenvironment will also be discussed.

• Interleukin-17
• T-lymphocytes
• Th17 cells
• Tumor microenvironment

• Esophageal squamous cell carcinoma (ESCC)
• Helper T cells
• Immunoregulation
• miR-21
• miR-29b

• Adult
• Aged
• Biomarkers
• Cell Line, Tumor
• Cytokines/metabolism
• Esophageal Squamous Cell Carcinoma/diagnosis
• Esophageal Squamous Cell Carcinoma/genetics
• Esophageal Squamous Cell Carcinoma/immunology
• Esophageal Squamous Cell Carcinoma/therapy
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Immunomodulation/genetics
• Male
• MicroRNAs/genetics
• Middle Aged
• ROC Curve
• T-Lymphocyte Subsets/immunology
• T-Lymphocyte Subsets/metabolism
• T-Lymphocytes, Helper-Inducer/immunology
• T-Lymphocytes, Helper-Inducer/metabolism

• Th17 cells
• Treg cells
• tumor
• tumor immunology
• tumor microenvironment

• Black raspberries
• DNA microarray
• NMBA
• inflammatory response
• rat preneoplastic esophagi

• R01 CA103180 NCI NIH HHS
• R01 CA148818 NCI NIH HHS

Esophageal squamous cell carcinoma (ESCC) is the most common esophageal cancer associated with poor prognosis. We detected the expression of C-C motif chemokine receptor 6 (CCR6) and epithelial-to-mesenchymal transition (EMT) markers in esophageal tissues/cells, and evaluated the effects of CCR6 on ESCC cells proliferation, migration and invasion in response to C-C motif chemokine ligand 20 (CCL20) treatment. Our data showed CCR6 was highly expressed in ESCC cell lines (ECA-109 and TE-1), whereas kept in a low expression in normal cell lines HEEC (P < 0.001). CCL20 stimulus induced a significant decrease in the proliferation ability of ESCC (P < 0.05). The healing speed of CCL20 group was significantly higher than control in ECA-109 (P < 0.01), whereas significantly lower in αCCR6+CCL20 group than CCL20 group (P < 0.05).The number of cells permeabling through the polycarbonate membrane in CCL20 group was higher than control (P < 0.01). The cell number in αCCR6+CCL20 group was significantly reduced compared to CCL20 group in ECA-109 (P < 0.05). Moreover, after CCL20 stimulated in ECA-109, both mRNA and protein level of E-cadherin significantly decreased compared to control, while Vimentin was significantly higher. In αCCR6+CCL20 group, mRNA and protein level of E-cadherin significantly increased compared to CCL20 group, while Vimentin was much lower than CCL20 group. There was no significant difference in TE-1. In summary, high expression of CCR6 existed in the lymph node metastasis and TNM stage of ESCC. CCR6 play an important role in the regulation of tumor cell proliferation, invasion and migration. CCR6 may participate in regulating the occurrence of EMT in ESCC.

• C-C motif chemokine receptor 6 (CCR6)
• epithelial-to-mesenchymal transition (EMT)
• esophageal squamous cell carcinoma (ESCC)
• lymph node metastasis

• CCR4 antagonist
• Endocytosis
• Receptor internalisation

Chemokines belong to a superfamily of small, cytokine-like proteins, which induce multiple physiological functions, particularly cytoskeletal rearrangement and compartment-specific migration through their interaction with G-protein-coupled receptors. Chemokines and their receptors have been widely acknowledged as essential and selective mediators in leukocyte migration in inflammatory response. It is now established that the chemokine/chemokine receptor system is also used by cancer cells to direct lymphatic and haematogenous spreading and additionally has an impact on the site of metastatic growth of different tumours. In recent years an increasing number of studies have drawn attention to CC-chemokine cysteine motif chemokine ligand 20 (CCL20) and its physiological sole receptor CCR6 to play a role in the onset, development and metastatic spread of various gastrointestinal cancer entities. Among various cancer types CCR6 was also demonstrated to be significantly overexpressed in colorectal cancer (CRC) and stimulation by its physiological ligand CCL20 has been reported to promote CRC cell proliferation and migration in vitro. Further, the CCL20/CCR6 system apparently plays a role in the organ-selective liver metastasis of CRC. Here we review the literature on expression patterns of CCL20 and CCR6 and their physiological interactions as well as the currently presumed role of CCL20 and CCR6 in the formation of CRC and the development of liver metastasis, providing a potential basis for novel treatment strategies.

• Chemokine/chemokine receptor pair
• CCR6
• Chemokine ligand 20
• Colorectal cancer
• Metastasis
• Liver

• Antineoplastic Agents/therapeutic use
• Cell Movement
• Cell Proliferation
• Chemokine CCL20/antagonists & inhibitors
• Chemokine CCL20/metabolism
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/pathology
• Humans
• Ligands
• Liver Neoplasms/drug therapy
• Liver Neoplasms/metabolism
• Liver Neoplasms/secondary
• Molecular Targeted Therapy
• Receptors, CCR6/antagonists & inhibitors
• Receptors, CCR6/metabolism
• Signal Transduction

Interleukin–23 (IL–23) is a conventional proinflammatory cytokine that plays a role in tumor progression by inducing inflammation in the tumor microenvironment. However, the role of IL–23 in thyroid cancer migration and invasion remains unclear. In the present study, we observed that the treatment with IL–23, induced migration and invasion in human thyroid cancer cells. Additional data demonstrate that SOCS4 negatively regulates IL-23-mediated migration and invasion. On investigating the mechanisms involved in IL–23 mediated migration and invasion, we observed that miR–25 promotes the migration and invasion of thyroid cancer cells by directly binding to the 3′-UTR of SOCS4 that leads to the inhibition of SOCS4. In addition, we also demonstrated that IL–23 increases miR–25 expression levels, and overexpressed miR–25 is involved in IL-23-associated SOCS4 inhibition and cell migration and invasion. Together, our data suggest that IL–23 induces migration and invasion in thyroid cancer cells by mediating the miR–25/SOCS4 signaling pathway.

• 3' Untranslated Regions
• Adult
• Cell Movement/drug effects
• DNA, Neoplasm/metabolism
• Female
• Gene Expression Regulation, Neoplastic/genetics
• Gene Expression Regulation, Neoplastic/physiology
• Humans
• Interleukin-23/pharmacology
• Male
• MicroRNAs/physiology
• Middle Aged
• Neoplasm Invasiveness/physiopathology
• RNA, Small Interfering/genetics
• Real-Time Polymerase Chain Reaction
• Signal Transduction
• Suppressor of Cytokine Signaling Proteins/biosynthesis
• Suppressor of Cytokine Signaling Proteins/genetics
• Suppressor of Cytokine Signaling Proteins/physiology
• Thyroid Neoplasms/pathology
• Tumor Cells, Cultured
• Up-Regulation

• CCL5
• CXCL10
• T lymphocyte
• chemotaxis
• esophageal squamous cell carcinoma

• CD8 Antigens/genetics
• CD8 Antigens/metabolism
• CD8-Positive T-Lymphocytes/metabolism
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/metabolism
• Cell Movement/genetics
• Chemokine CCL5/genetics
• Chemokine CCL5/metabolism
• Chemokine CXCL10/genetics
• Chemokine CXCL10/metabolism
• Esophageal Neoplasms/genetics
• Esophageal Neoplasms/metabolism
• Female
• Gene Expression Regulation, Neoplastic
• Granzymes/genetics
• Granzymes/metabolism
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Reverse Transcriptase Polymerase Chain Reaction

• P30 CA060553 NCI NIH HHS

Our previous studies suggest that Th17 cells accumulate within tumor tissues and correlate with recurrence of cervical cancer patients. However, the source of the increased tumor-infiltrating Th17 cells remains poorly understood. We investigated the prevalence, phenotype and trafficking property of Th17 cells in patients with cervical cancer. Our results showed that Th17 cells highly aggregated within tumor tissues in an activated phenotype with markedly increased expression of CCR6. Correspondingly, level of CCL20 in the tumor tissues was significantly higher than that in non-tumor and normal control tissues, and strongly positively associated with Th17 cells. Further, in vitro migration assay showed CCL20 had effective chemotaxis to circulating Th17 cells. In conclusion, Th17 cells are recruited into tumor tissues preferentially through CCR6-CCL20 pathway, which can serve as a novel therapeutic target for cervical cancer.

• Chemokine CCL20/metabolism
• Chemotaxis
• Female
• Humans
• Phenotype
• Receptors, CCR6/metabolism
• Th17 Cells/cytology
• Th17 Cells/immunology
• Uterine Cervical Neoplasms/immunology
• Uterine Cervical Neoplasms/metabolism

As the eighth most common malignant tumour worldwide, oesophageal cancer (OC) is often diagnosed during the metastasis of its advanced stage. Interleukin (IL)-23 is an immunomodulatory cytokine that has recently been identified as a cancer-associated factor. However, the role of IL-23 in the evolution of OC remains unclear. In the present study, we found that IL-23 was significantly expressed in the tumours of OC patients suffering metastasis and demonstrated that IL-23 contributed to epithelial-mesenchymal transition (EMT) through the Wnt/β-catenin pathway, promoting the migration and invasion of OC cells. In conclusion, IL-23 plays a pivotal role in the development of OC via EMT.

• CCL20
• Docetaxel
• NSCLC

This is the first study evaluating the interactions of human adipose tissue derived stem cells (ADSCs) and human squamous cell carcinoma cells (SCCs), with regard to a prospective cell-based skin regenerative therapy and a thereby unintended co-localization of ADSCs and SCCs.

ADSCs were co-cultured with A431-SCCs and primary SCCs (pSCCs) in a transwell system, and cell-cell interactions were analyzed by assessing doubling time, migration and invasion, angiogenesis, quantitative real time PCR of 229 tumor associated genes, and multiplex protein assays of 20 chemokines and growth factors and eight matrix metalloproteinases (MMPS). Results of co-culture were compared to those of the respective mono-culture.

ADSCs’ proliferation on the plate was significantly increased when co-cultured with A431-SCCs (P = 0.038). PSCCs and ADSCs significantly decreased their proliferation in co-culture if cultured on the plate (P <0.001 and P = 0.03). The migration of pSCC was significantly increased in co-culture (P = 0.009), as well as that of ADSCs in A431-SCC-co-culture (P = 0.012). The invasive behavior of pSCCs and A431-SCCs was significantly increased in co-culture by a mean of 33% and 35%, respectively (P = 0.038 and P <0.001). Furthermore, conditioned media from co-cultured ADSC-A431-SCCs and co-cultured ADSCs-pSCCs induced tube formation in an angiogenesis assay in vitro.

In A431-SCC-co-culture 36 genes were up- and 6 were down-regulated in ADSCs, in A431-SCCs 14 genes were up- and 8 genes were down-regulated. In pSCCs-co-culture 36 genes were up-regulated in ADSCs, two were down-regulated, one gene was up-regulated in pSCC, and three genes were down-regulated. Protein expression analysis revealed that three proteins were exclusively produced in co-culture (CXCL9, IL-1b, and MMP-7). In A431-SCC-co-culture the concentration of 17 proteins was significantly increased compared to the ADSCs mono-culture (2.8- to 357-fold), and 15 proteins were expressed more highly (2.8- to 1,527-fold) compared to the A431-SCCs mono-culture. In pSCC-co-culture the concentration of 10 proteins was increased compared to ADSCs-mono-culture (2.5- to 77-fold) and that of 15 proteins was increased compared to pSCC mono-culture (2.6- to 480-fold).

This is the first study evaluating the possible interactions of primary human ADSCs with human SCCs, pointing towards a doubtlessly increased oncological risk, which should not be neglected when considering a clinical use of isolated human ADSCs in skin regenerative therapies.