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TH17 cells in tumour immunity and immunotherapy

Stephanie Downs-Canner, Sara Berkey, Greg M Delgoffe, Robert P Edwards, Tyler Curiel, Kunle Odunsi, David L Bartlett, Nataša Obermajer
Th17 and regulatory T (Treg) cells are integral in maintaining immune homeostasis and Th17-Treg imbalance is associated with inflammatory immunosuppression in cancer. Here we show that Th17 cells are a source of tumour-induced Foxp3(+) cells. In addition to natural (n)Treg and induced (i)Treg cells that develop from naive precursors, suppressive IL-17A(+)Foxp3(+) and ex-Th17 Foxp3(+) cells are converted from IL-17A(+)Foxp3(neg) cells in tumour-bearing mice. Metabolic phenotyping of Foxp3-expressing IL-17A(+), ex-Th17 and iTreg cells demonstrates the dissociation between the metabolic fitness and the suppressive function of Foxp3-expressing Treg cell subsets...
March 14, 2017: Nature Communications
Damya Laoui, Jiri Keirsse, Yannick Morias, Eva Van Overmeire, Xenia Geeraerts, Yvon Elkrim, Mate Kiss, Evangelia Bolli, Qods Lahmar, Dorine Sichien, Jens Serneels, Charlotte L Scott, Louis Boon, Patrick De Baetselier, Massimiliano Mazzone, Martin Guilliams, Jo A Van Ginderachter
Various steady state and inflamed tissues have been shown to contain a heterogeneous DC population consisting of developmentally distinct subsets, including cDC1s, cDC2s and monocyte-derived DCs, displaying differential functional specializations. The identification of functionally distinct tumour-associated DC (TADC) subpopulations could prove essential for the understanding of basic TADC biology and for envisaging targeted immunotherapies. We demonstrate that multiple mouse tumours as well as human tumours harbour ontogenically discrete TADC subsets...
December 23, 2016: Nature Communications
Yong Zhang, Xiaoyan Hu, Yue Hu, Kai Teng, Kai Zhang, Yamei Zheng, Xiaohua Hong, Kunwu Yu, Yan Wang, Li Liu
BACKGROUND: Agonistic CD40 antibodies have been demonstrated to activate antigen-presenting cells (APCs) and enhance antitumour T cell responses, thereby providing a new therapeutic option in cancer immunotherapy. In agonistic CD40 antibody-mediated inflammatory responses, a novel subset of E-cadherin + dendritic cells (DCs) has been identified, and little is known about the role of these DCs in tumour immunity. This study investigated the effect of anti-CD40-mediated inflammatory E-cadherin + DCs in murine Lewis lung carcinoma (LLC)...
2015: Journal of Experimental & Clinical Cancer Research: CR
Joanna Domagała-Kulawik, Iwona Osińska
Lung cancer is the main cause of cancer death worldwide. An advanced stage of the disease at the time of diagnosis, observed in the majority of cases, does not allow for introduction of radical treatment or makes the treatment ineffective. Lung cancer as a solid tumour with a very low antigenicity escapes immune surveillance, and cytotoxic cells attack. Cytotoxic lymphocytes play a key role in anticancer defence, but the population of these cells individually differs. Many suppressor and regulatory mechanisms inhibit the recognition of tumour antigens by dendritic and cytotoxic cell activation...
2014: Pneumonologia i Alergologia Polska
C-J Shen, Z-H Yuan, Y-X Liu, G-Y Hu
OBJECTIVE: T helper 17 (Th17) cells play important roles in adaptive immunity and are involved in several inflammatory and autoimmune diseases, but little is known about their role in tumour immunity. The current study investigated the involvement of Th17 cells in multiple myeloma. METHODS: Flow cytometry was used to investigate the frequencies of Th17 cells in peripheral blood mononuclear cells from 30 patients with multiple myeloma and from 14 healthy control subjects...
2012: Journal of International Medical Research
E Maniati, R Soper, T Hagemann
The role of interleukin (IL)-17 and the IL-17-producing T helper (Th)17 cells in cancer has recently become the focus of extensive investigation. An expanding body of literature implicates Th17 cells and their hallmark cytokine in both pro- and anti-tumourigenic processes. In this review we describe their biological activities and outline the reciprocal interactions between Th17 cells and other cells of the immune system. We also discuss the evidence regarding their dual role in the tumour microenvironment...
October 21, 2010: Oncogene
Ida Ricciardelli, Keith J Lindley, Marco Londei, Sonia Quaratino
Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Its pathogenesis is not completely understood, though the prevailing model is that the intestinal flora drives a strong intestinal T helper 1 (Th1)/Th17 type immune response and inflammation in the genetically susceptible host. This leads to overly aggressive T-cell responses to normal bacteria causing tissue damage. Intestinal homeostasis and maintenance of tolerance to harmless antigens in the intestine has been shown to be maintained by CD4+ CD25+ T regulatory cells (Treg) in animal models of inflammatory bowel diseases...
October 2008: Immunology
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