Dataset Information

Roles of regulatory T cells in cancer immunity.

ABSTRACT: CD4(+) regulatory T cells (Tregs) expressing the transcription factor FoxP3 are highly immune suppressive and play central roles in the maintenance of self-tolerance and immune homeostasis, yet in malignant tumors they promote tumor progression by suppressing effective antitumor immunity. Indeed, higher infiltration by Tregs is observed in tumor tissues, and their depletion augments antitumor immune responses in animal models. Additionally, increased numbers of Tregs and, in particular, decreased ratios of CD8(+) T cells to Tregs among tumor-infiltrating lymphocytes are correlated with poor prognosis in various types of human cancers. The recent success of cancer immunotherapy represented by immune checkpoint blockade has provided a new insight in cancer treatment, yet more than half of the treated patients did not experience clinical benefits. Identifying biomarkers that predict clinical responses and developing novel immunotherapies are therefore urgently required. Cancer patients whose tumors contain a large number of neoantigens stemming from gene mutations, which have not been previously recognized by the immune system, provoke strong antitumor T-cell responses associated with clinical responses following immune checkpoint blockade, depending on the resistance to Treg-mediated suppression. Thus, integration of a strategy restricting Treg-mediated immune suppression may expand the therapeutic spectrum of cancer immunotherapy towards patients with a lower number of neoantigens. In this review, we address the current understanding of Treg-mediated immune suppressive mechanisms in cancer, the involvement of Tregs in cancer immunotherapy, and strategies for effective and tolerable Treg-targeted therapy.

SUBMITTER: Takeuchi Y

PROVIDER: S-EPMC4986235 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Roles of regulatory T cells in cancer immunity.

Takeuchi Yoshiko Y Nishikawa Hiroyoshi H

International immunology 20160509 8

CD4(+) regulatory T cells (Tregs) expressing the transcription factor FoxP3 are highly immune suppressive and play central roles in the maintenance of self-tolerance and immune homeostasis, yet in malignant tumors they promote tumor progression by suppressing effective antitumor immunity. Indeed, higher infiltration by Tregs is observed in tumor tissues, and their depletion augments antitumor immune responses in animal models. Additionally, increased numbers of Tregs and, in particular, decrease ...[more]

PMID: 27160722

Similar Datasets

Project description:BackgroundTumors are characterized by extracellular matrix (ECM) remodeling and stiffening. The ECM has been recognized as an important determinant of breast cancer progression and prognosis. Recent studies have revealed a strong link between ECM remodeling and immune cell infiltration in a variety of tumor types. However, the landscape and specific regulatory mechanisms between ECM and immune microenvironment in breast cancer have not been fully understood.MethodsUsing genomic data and clinical information of breast cancer patients obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we conducted an extensive multi-omics analysis to explore the heterogeneity and prognostic significance of the ECM microenvironment. Masson and Sirius red staining were applied to quantify the contents of collagen in the ECM microenvironment. Tissue immunofluorescence (IF) staining was applied to identify T helper (Th) cells.ResultsWe classified breast cancer patients into two ECM-clusters and three gene-clusters by consensus clustering. Significant heterogeneity in prognosis and immune cell infiltration have been found in these distinct clusters. Specifically, in the ECM-cluster with better prognosis, the expression levels of Th2 and regulatory T (Treg) cells were reduced, while the Th1, Th17 and T follicular helper (Tfh) cells-associated activities were significantly enhanced. The correlations between ECM characteristics and Th cells infiltration were then validated by clinical tissue samples from our hospital. The ECM-associated prognostic model was then constructed by 10 core prognostic genes and stratified breast cancer patients into two risk groups. Kaplan-Meier analysis showed that the overall survival (OS) of breast cancer patients in the high-risk group was significantly worse than that of the low-risk group. The risk scores for breast cancer patients obtained from our prognostic model were further confirmed to be associated with immune cell infiltration, tumor mutation burden (TMB) and stem cell indexes. Finally, the half-maximal inhibitory concentration (IC50) values of antitumor agents for patients in different risk groups were calculated to provide references for therapy targeting distinct ECM characteristics.ConclusionOur findings identify a novel strategy for breast cancer subtyping based on the ECM characterization and reveal the regulatory roles of Th cells in ECM remodeling. Targeting ECM remodeling and Th cells hold potential to be a therapeutic alternative for breast cancer in the future.

Dataset Information

Roles of regulatory T cells in cancer immunity.

Publications

Roles of regulatory T cells in cancer immunity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets