scholarly journals FOXP3 in Melanoma with Regression: Between Tumoral Expression and Regulatory T Cell Upregulation

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Mirela Cioplea ◽  
Luciana Nichita ◽  
Daniela Georgescu ◽  
Liana Sticlaru ◽  
Alexandra Cioroianu ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Regulatory T Cells ◽  
Tumor Cells ◽  
Retrospective Cohort ◽  
Poor Prognosis ◽  
Tumor Regression ◽  
Foxp3 Expression ◽  
Immune Defense ◽  
Stromal Microenvironment

Cutaneous melanoma is a significant immunogenic tumoral model, the most frequently described immune phenomenon being tumor regression, as a result of the interaction of tumoral antigens and stromal microenvironment. We present a retrospective cohort study including 52 cases of melanoma with regression. There were evaluated correlations of the most important prognostic factors (Breslow depth and mitotic index) with FOXP3 expression in tumor cells and with the presence of regulatory T cells and dendritic cells in the tumoral stroma. FOXP3 expression in tumor cells seems an independent factor of poor prognosis in melanoma, while regression areas are characterized by a high number of dendritic cells and a low number of regulatory T cells. FOXP3 is probably a useful therapeutical target in melanoma, since inhibition of FOXP3-positive tumor clones and of regulatory T cells could eliminate the ability of tumor cells to escape the immune defense of the host.

scholarly journals Tumor cells convert immature myeloid dendritic cells into TGF-β–secreting cells inducing CD4+CD25+ regulatory T cell proliferation

2005 ◽  
Vol 202 (7) ◽  
pp. 919-929 ◽  
Author(s):  
François Ghiringhelli ◽  
Pierre E. Puig ◽  
Stephan Roux ◽  
Arnaud Parcellier ◽  
Elise Schmitt ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
Dendritic Cells ◽  
Regulatory T Cells ◽  
Tumor Cells ◽  
Transforming Growth Factor ◽  
Dependent Manner ◽  
Myeloid Dendritic Cells ◽  
Β Receptor ◽  
Necessary And Sufficient

The mechanisms through which regulatory T cells accumulate in lymphoid organs of tumor-bearing hosts remain elusive. Our experiments indicate that the accumulation of CD4+CD25+ regulatory T cells (T reg cells) expressing FoxP3 and exhibiting immunosuppressive function originates from the proliferation of naturally occurring CD25+ T cells and requires signaling through transforming growth factor (TGF)–β receptor II. During tumor progression, a subset of dendritic cells (DCs) exhibiting a myeloid immature phenotype is recruited to draining lymph nodes. This DC subset selectively promotes the proliferation of T reg cells in a TGF-β–dependent manner in mice and rats. Tumor cells are necessary and sufficient to convert DCs into regulatory cells that secrete bioactive TGF-β and stimulate T reg cell proliferation. In conclusion, tumor expansion can stimulate T reg cells via a specific DC subset.

scholarly journals Plasmacytoid Dendritic Cells and ICOS+ Regulatory T Cells Predict Poor Prognosis in Gastric Cancer: A Pilot Study

2019 ◽  
Vol 10 (26) ◽  
pp. 6711-6715 ◽  
Author(s):  
Xiaosun Liu ◽  
Hang Yu ◽  
Chongxian Yan ◽  
Ying Mei ◽  
Caizhao Lin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Dendritic Cells ◽  
Pilot Study ◽  
Regulatory T Cells ◽  
Poor Prognosis ◽  
Plasmacytoid Dendritic Cells

scholarly journals Dendritic Cells Loaded with Stressed Tumor Cells Elicit Long-Lasting Protective Tumor Immunity in Mice Depleted of CD4+CD25+Regulatory T Cells

2004 ◽  
Vol 174 (1) ◽  
pp. 90-98 ◽  
Author(s):  
Simon J. Prasad ◽  
Kathryn J. Farrand ◽  
Stephanie A. Matthews ◽  
Joe H. Chang ◽  
Rebecca S. McHugh ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Regulatory T Cells ◽  
Tumor Cells ◽  
Tumor Immunity

scholarly journals Infected site-restricted Foxp3+ natural regulatory T cells are specific for microbial antigens

2006 ◽  
Vol 203 (3) ◽  
pp. 777-788 ◽  
Author(s):  
Isabelle J. Suffia ◽  
Stacie K. Reckling ◽  
Ciriaco A. Piccirillo ◽  
Romina S. Goldszmid ◽  
Yasmine Belkaid
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Regulatory T Cells ◽  
Chronic Infection ◽  
Leishmania Major ◽  
Foxp3 Expression ◽  
Antigen Recognition ◽  
Antigenic Specificity ◽  
Self Antigen

Natural regulatory T (T reg) cells are involved in control of the immune response, including response to pathogens. Previous work has demonstrated that the repertoire of natural T reg cells may be biased toward self-antigen recognition. Whether they also recognize foreign antigens and how this recognition contributes to their function remain unknown. Our studies addressed the antigenic specificity of natural T reg cells that accumulate at sites of chronic infection with Leishmania major in mice. Our results support the idea that natural T reg cells are able to respond specifically to foreign antigens in that they strongly proliferate in response to Leishmania-infected dendritic cells, they maintain Foxp3 expression, and Leishmania-specific T reg cell lines can be generated from infected mice. Surprisingly, the majority of natural T reg cells at the infected site are Leishmania specific. Further, we showed that parasite-specific natural T reg cells are restricted to sites of infection and that their survival is strictly dependent on parasite persistence.

scholarly journals Alpha-Fetoprotein- and CD40Ligand-Expressing Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3375
Author(s):  
Annabelle Vogt ◽  
Farsaneh Sadeghlar ◽  
Tiyasha H. Ayub ◽  
Carlo Schneider ◽  
Christian Möhring ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Dendritic Cells ◽  
Tumor Regression ◽  
Combined Therapy ◽  
Term Survival ◽  
Effector Cells ◽  
Tumor Environment ◽  
The Impact

Dendritic cells (DC) as professional antigen presenting cells are able to prime T-cells against the tumor-associated antigen α-fetoprotein (AFP) for immunotherapy of hepatocellular carcinoma (HCC). However, a strong immunosuppressive tumor environment limits their efficacy in patients. The co-stimulation with CD40Ligand (CD40L) is critical in the maturation of DC and T-cell priming. In this study, the impact of intratumoral (i.t.) CD40L-expressing DC to improve vaccination with murine (m)AFP-transduced DC (Ad-mAFP-DC) was analyzed in subcutaneous (s.c.) and orthotopic murine HCC. Murine DC were adenovirally transduced with Ad-mAFP or Ad-CD40L. Hepa129-mAFP-cells were injected into the right flank or the liver of C3H-mice to induce subcutaneous (s.c.) and orthotopic HCC. For treatments, 106 Ad-mAFP-transduced DC were inoculated s.c. followed by 106 CD40L-expressing DC injected intratumorally (i.t.). S.c. inoculation with Ad-mAFP-transduced DC, as vaccine, induced a delay of tumor-growth of AFP-positive HCC compared to controls. When s.c.-inoculation of Ad-mAFP-DC was combined with i.t.-application of Ad-CD40L-DC synergistic antitumoral effects were observed and complete remissions and long-term survival in 62% of tumor-bearing animals were achieved. Analysis of the tumor environment at different time points revealed that s.c.-vaccination with Ad-mAFP-DC seems to stimulate tumor-specific effector cells, allowing an earlier recruitment of effector T-cells and a Th1 shift within the tumors. After i.t. co-stimulation with Ad-CD40L-DC, production of Th1-cytokines was strongly increased and accompanied by a robust tumor infiltration of mature DC, activated CD4+-, CD8+-T-cells as well as reduction of regulatory T-cells. Moreover, Ad-CD40L-DC induced tumor cell apoptosis. Intratumoral co-stimulation with CD40L-expressing DC significantly improves vaccination with Ad-mAFP-DC in pre-established HCC in vivo. Combined therapy caused an early and strong Th1-shift in the tumor environment as well as higher tumor apoptosis, leading to synergistic tumor regression of HCC. Thus, CD40L co-stimulation represents a promising tool for improving DC-based immunotherapy of HCC.

scholarly journals Secretome screening reveals immunomodulating functions of IFNα-7, PAP and GDF-7 on regulatory T-cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mei Ding ◽  
Rajneesh Malhotra ◽  
Tomas Ottosson ◽  
Magnus Lundqvist ◽  
Aman Mebrahtu ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cell Function ◽  
Foxp3 Expression ◽  
Treg Cells ◽  
Secreted Proteins ◽  
External Stimulation ◽  
Marker Proteins ◽  
Positive Regulators ◽  
Conformational Model

AbstractRegulatory T cells (Tregs) are the key cells regulating peripheral autoreactive T lymphocytes. Tregs exert their function by suppressing effector T cells. Tregs have been shown to play essential roles in the control of a variety of physiological and pathological immune responses. However, Tregs are unstable and can lose the expression of FOXP3 and suppressive functions as a consequence of outer stimuli. Available literature suggests that secreted proteins regulate Treg functional states, such as differentiation, proliferation and suppressive function. Identification of secreted proteins that affect Treg cell function are highly interesting for both therapeutic and diagnostic purposes in either hyperactive or immunosuppressed populations. Here, we report a phenotypic screening of a human secretome library in human Treg cells utilising a high throughput flow cytometry technology. Screening a library of 575 secreted proteins allowed us to identify proteins stabilising or destabilising the Treg phenotype as suggested by changes in expression of Treg marker proteins FOXP3 and/or CTLA4. Four proteins including GDF-7, IL-10, PAP and IFNα-7 were identified as positive regulators that increased FOXP3 and/or CTLA4 expression. PAP is a phosphatase. A catalytic-dead version of the protein did not induce an increase in FOXP3 expression. Ten interferon proteins were identified as negative regulators that reduced the expression of both CTLA4 and FOXP3, without affecting cell viability. A transcriptomics analysis supported the differential effect on Tregs of IFNα-7 versus other IFNα proteins, indicating differences in JAK/STAT signaling. A conformational model experiment confirmed a tenfold reduction in IFNAR-mediated ISG transcription for IFNα-7 compared to IFNα-10. This further strengthened the theory of a shift in downstream messaging upon external stimulation. As a summary, we have identified four positive regulators of FOXP3 and/or CTLA4 expression. Further exploration of these Treg modulators and their method of action has the potential to aid the discovery of novel therapies for both autoimmune and infectious diseases as well as for cancer.

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