Regulatory T cells (Treg cells) are important for preventing autoimmunity and maintaining tissue homeostasis, but whether Treg cells can adopt tissue- or immune-context-specific suppressive mechanisms is unclear. Here, we found that the enzyme hydroxyprostaglandin dehydrogenase (HPGD), which catabolizes prostaglandin E2 (PGE2) into the metabolite 15-keto PGE2, was highly expressed in Treg cells, particularly those in visceral adipose tissue (VAT). Nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ)-induced HPGD expression in VAT Treg cells, and consequential Treg-cell-mediated generation of 15-keto PGE2 suppressed conventional T cell activation and proliferation. Conditional deletion of Hpgd in mouse Treg cells resulted in the accumulation of functionally impaired Treg cells specifically in VAT, causing local inflammation and systemic insulin resistance. Consistent with this mechanism, humans with type 2 diabetes showed decreased HPGD expression in Treg cells. These data indicate that HPGD-mediated suppression is a tissue- and context-dependent suppressive mechanism used by Treg cells to maintain adipose tissue homeostasis.
Copyright © 2019 Elsevier Inc. All rights reserved.

Thermal ablation therapy has recently emerged as a promising noninvasive treatment modality for localized solid malignancies. Except its direct tumor-cell-killing effect on local tumor tissues, the immunomodulatory effect has also long been noticed which too has substantial effect on clinical outcome, but it is complicated. Though much has been investigated and rich evidences have been achieved, the fundamental state and profile of immunomodulation by thermal ablation in cancer patients, its exact mechanism, especially the systematic mechanism, and its effect on antitumor immunity remain unclear.
In this study, we dynamically monitored the immunomodulation by thermal ablation through combined analysis of peripheral lymphocyte populations, functional T cell subtype Th1 (CD3+CD4+IFN-r+), Th2 (CD3+CD4+IL-4+), Tc1 (CD3+CD8+IFN-r+), Tc2 (CD3+CD8+IL-4+) and mRNA expression of several immune-active and -suppressive molecules including CD25, CD28, cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1, Foxp3, transforming growth factor beta (TGF-β) and interleukin (IL-10) in 16 cancer patients.
The results show that local cancer thermal ablation modulated the cellular immunity characterized by obviously downregulation of regulatory T cells (Treg) and cytotoxicity T cells followed by CD4, CD8 and suppressor T cells (Ts), but upregulation of natural killer (NK) cells and mRNA expression of TGF-β and IL-10, suggesting a slight inhibition of the cellular immunity which may affect antitumor immunity.
We suggest a further immunomodulation therapy after thermal therapy for recovering a Th1- and Tc1-dominant immune response for pursuing a better long-term antitumor immunity.
© 2018 John Wiley & Sons Australia, Ltd.

In the present case study, an immunomodulatory regimen for cancer prevention is reported. A patient with an abnormally high level of the tumor markers, carbohydrate antigen-724 (CA724), CA19-9 and carcinoembryonic antigen (CEA), although without any detectable tumor, was treated with an immunomodulatory therapy featuring an infusion of cytokine-induced autologous killer cells (CIKs) at the request of the patient. Following the therapy, the three tumor markers rapidly decreased to below the normal reference level, although there still were slight fluctuations within a narrow range frequently. The patient was monitored for 21 months to the present day and no abnormality was observed. The results indicated that this therapy may be applied as a novel strategy that is effective and reliable for cancer prevention. As there is no promising regimen for the prevention of malignancies to date, such a treatment may become a major cancer prophylactic regimen, particularly for patients who are at a high risk of cancer.

We previously demonstrated the presence of leucocytes in the adenoid surface secretion with the ability of immunoglobulin A (IgA), IgM and IgG production as well as production of cells with phagocytic capacity. In the present study, we investigated the presence of activated T cells in the secretion. Adenoid surface secretion from 12 children subjected to adenoidectomy was obtained with an imprint method. From six children, peripheral blood was also obtained. By flow cytometry, the number of lymphocytes, granulocytes, epithelial cells and red blood cells was analysed as well as the expression on lymphocyte subsets of the following antigens: CD3, CD4, CD8, CD19, CD25, CD38, CD45RO, CD45RA, HLA-DR, TcRgd, CD161 and l-selectin. The majority of T cells were activated and to a significantly higher degree were CD45RO+, CD161+ and l-selectin-, as compared with the corresponding peripheral blood. The median percentage of B cells and T cells in the secretion were 81 and 13%, respectively. In conclusion, the proportion of B and T cells in the adenoid surface secretion is significantly different as compared with the peripheral blood. The T cells in the adenoid surface secretion are to a high degree activated. The results suggest that the leucocytes in the surface secretion are part of the mucosal defence.