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Intratumoral TFR cells curtail anti-PD-1 treatment efficacy

ABSTRACT: Follicular regulatory T cells (TFR cells) and their functional role in cancer have been completely disregarded so far. Our data identify that as a critical oversight, as these cells account for a substantial proportion of tumor-infiltrating CD4+ T cells

ORGANISM(S): Homo sapiens

PROVIDER: GSE145691 | GEO | 2022/06/01

REPOSITORIES: GEO

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Intratumoral TFR cells curtail anti-PD-1 treatment efficacy [mouse]

Project description:Follicular regulatory T cells (TFR cells) and their functional role in cancer have been completely disregarded so far. Our data identify that as a critical oversight, as these cells account for a substantial proportion of tumor-infiltrating CD4+ T cells

2021-05-03 | GSE132296 | GEO

Intratumoral TFR cells curtail anti-PD-1 treatment efficacy [human]

2021-05-03 | GSE132295 | GEO

Intratumoral TFR cells curtail anti-PD-1 treatment efficacy

Project description:Intratumoral TFR cells curtail anti-PD-1 treatment efficacy

| PRJNA547551 | ENA

Intratumoral TFR cells curtail anti-PD-1 treatment efficacy

Project description:Intratumoral TFR cells curtail anti-PD-1 treatment efficacy

| PRJNA607958 | ENA

Intratumoral TFR cells curtail anti-PD-1 treatment efficacy [human]

Project description:Intratumoral TFR cells curtail anti-PD-1 treatment efficacy [human]

| PRJNA547554 | ENA

Intratumoral TFR cells curtail anti-PD-1 treatment efficacy [mouse]

Project description:Intratumoral TFR cells curtail anti-PD-1 treatment efficacy [mouse]

| PRJNA547567 | ENA

Intratumoral TFR cells curtail anti-PD-1 treatment efficacy

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-05-03 | GSE132297 | GEO

Intratumoral follicular regulatory T cells curtail anti-PD-1 treatment efficacy.

Project description:Immune-checkpoint blockade (ICB) has shown remarkable clinical success in boosting antitumor immunity. However, the breadth of its cellular targets and specific mode of action remain elusive. We find that tumor-infiltrating follicular regulatory T (TFR) cells are prevalent in tumor tissues of several cancer types. They are primarily located within tertiary lymphoid structures and exhibit superior suppressive capacity and in vivo persistence as compared with regulatory T cells, with which they share a clonal and developmental relationship. In syngeneic tumor models, anti-PD-1 treatment increases the number of tumor-infiltrating TFR cells. Both TFR cell deficiency and the depletion of TFR cells with anti-CTLA-4 before anti-PD-1 treatment improve tumor control in mice. Notably, in a cohort of 271 patients with melanoma, treatment with anti-CTLA-4 followed by anti-PD-1 at progression was associated with better a survival outcome than monotherapy with anti-PD-1 or anti-CTLA-4, anti-PD-1 followed by anti-CTLA-4 at progression or concomitant combination therapy.

| S-EPMC8434898 | biostudies-literature

Decreased TFR/TFH ratio in SIV-infected rhesus macaques may contribute to accumulation of TFH cells in chronic infection

Project description:T follicular helper cells (TFH) are critical for the development and maintenance of germinal centers (GC) and humoral immune responses. During chronic HIV/SIV infection TFH accumulate, possibly as a result of antigen persistence. The HIV/SIV-associated TFH expansion may also reflect lack of regulation by suppressive follicular regulatory CD4+ T-cells (TFR). TFR are natural regulatory T-cells (TREG) that migrate into the follicle and, similarly to TFH, up-regulate CXCR5, Bcl-6, and PD1. Here we identified TFR as CD4+CD25+FoxP3+CXCR5+PD1hiBcl-6+ within lymph nodes of rhesus macaques (RM) and confirmed their localization within the GC by immunohistochemistry. RNA sequencing showed that TFR exhibit a distinct transcriptional profile with shared features of both TFH and TREG, including intermediate expression of FoxP3, Bcl-6, PRDM1, IL-10, and IL-21. In healthy, SIV-uninfected RM, we observed a negative correlation between frequencies of TFR and both TFH and GC B-cells as well as levels of CD4+ T-cell proliferation. Following SIV infection, the TFR/TFH ratio was reduced with no change in the frequency of TREG or TFR within the total CD4+ T-cell pool. Finally, we examined whether higher levels of direct virus infection of TFR were responsible for their relative depletion post-SIV infection. We found that TFH, TFR and TREG sorted from SIV- infected RM harbor comparable levels of cell-associated viral DNA. Our data suggests that TFR may contribute to the regulation and proliferation of TFH and GC B-cells in vivo and that a decreased TFR/TFH ratio in chronic SIV infection may lead to unchecked expansion of both TFH and GC B-cells. TFR, TFH, TREG and bulk CD4 cells were sorted from spleens of 5 uninfected and 5 infected RM.

2015-09-02 | E-GEOD-69756 | biostudies-arrayexpress

Shared and unique features distinguishing follicular T helper (TFH) and regulatory (TFR) cells from peripheral lypmh node and Peyer's Patches [Agilent-048306]

Project description:Transcriptome analyses were done comparing gene regulation of TFH and TFR cells isolated from Peyer’s Patches (PP) and immunized peripheral lymph nodes (pLN) revealing many regulatory patterns common to all follicular cells. However, in contrast to TFH cells, the kinetic but also the extent of regulation regarding many genes was attenuated in pLN TFR cells when compared to those of PP. Additionally, PP but not pLN TFR cells were largely unresponsive to IL2 and expressed Il4 as well as Il21. Together with fundamental differences in gene expression that were found between cells of both compartments this emphasizes specific adaptations of follicular T cell functions to their micro-milieu.

2018-04-16 | GSE106490 | GEO

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