T Regulatory Cells and Priming the Suppressive Tumor Microenvironment

Paluskievicz, Christina; Cao, Xuefang; Abdi, Reza; Zheng, Pan; Liu, Yang; Bromberg, Jonathan S.

doi:10.3389/fimmu.2019.02453

Cited by 173 publications

(147 citation statements)

References 175 publications

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“…The up-regulation of CD44 observed in KIR2DL2/L3/S2+ CD8+ T cells will favor their interaction with VLA-4 integrin in order to facilitate their infiltration in the tumor [ 42 ] and their contact with dendritic and other immune cells [ 43 ]. This is particularly relevant since these cells also over-express CCR1 and CCR5, chemokine receptors for ligands secreted by tumor cells [ 40 , 44 ] which are shared with monocytes/macrophages, dendriticcells, and neutrophils. This could bring together T cells secreting notable amounts of IFNγ, TGBβ, IL32, and IL18RAP with myeloid/monocyte-derived cells in the tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling

Gimeno

Serrano-López

Campillo

et al. 2020

Cancers

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Killer-cell immunoglobulin-like receptors (KIR) are expressed by natural killer (NK) and effector T cells. Although KIR+ T cells accumulate in oncologic patients, their role in cancer immune response remains elusive. This study explored the role of KIR+CD8+ T cells in cancer immunosurveillance by analyzing their frequency at diagnosis in the blood of 249 patients (80 melanomas, 80 bladder cancers, and 89 ovarian cancers), their relationship with overall survival (OS) of patients, and their gene expression profiles. KIR2DL1+ CD8+ T cells expanded in the presence of HLA-C2-ligands in patients who survived, but it did not in patients who died. In contrast, presence of HLA-C1-ligands was associated with dose-dependent expansions of KIR2DL2/S2+ CD8+ T cells and with shorter OS. KIR interactions with their specific ligands profoundly impacted CD8+ T cell expression profiles, involving multiple signaling pathways, effector functions, the secretome, and consequently, the cellular microenvironment, which could impact their cancer immunosurveillance capacities. KIR2DL1/S1+ CD8+ T cells showed a gene expression signature related to efficient tumor immunosurveillance, whereas KIR2DL2/L3/S2+CD8+ T cells showed transcriptomic profiles related to suppressive anti-tumor responses. These results could be the basis for the discovery of new therapeutic targets so that the outcome of patients with cancer can be improved.

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Section: Discussionmentioning

confidence: 99%

KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling

Gimeno

Serrano-López

Campillo

et al. 2020

Cancers

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“…In physiologic conditions, they maintain self-tolerance by inhibiting T cell functions. Tregs are upregulated in cancer patients and contribute to creating an immunosuppressive microenvironment, favoring tumor progression [33][34][35]. Several studies were focused on correlating the increased amount of Tregs in cancer patients with TEV functions, analyzing if TEVs can directly affect this T cell population ( Figure 1A).…”

Section: Tevs and Regulatory T Cellsmentioning

confidence: 99%

Extracellular Vesicles and Tumor-Immune Escape: Biological Functions and Clinical Perspectives

Raimondo

Pucci

Alessandro

et al. 2020

IJMS

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The modulation of the immune system is one of the hallmarks of cancer. It is now widely described that cancer cells are able to evade the immune response and thus establish immune tolerance. The exploration of the mechanisms underlying this ability of cancer cells has always attracted the scientific community and is the basis for the development of new promising cancer therapies. Recent evidence has highlighted how extracellular vesicles (EVs) represent a mechanism by which cancer cells promote immune escape by inducing phenotypic changes on different immune cell populations. In this review, we will discuss the recent findings on the role of tumor-derived extracellular vesicles (TEVs) in regulating immune checkpoints, focusing on the PD-L1/PD-1 axis.

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“…[16][17][18] The Treg cells are not only restricted to these functions but also exert an important role in tumor immunity. 19,20 Although their immunosuppressive property helps to prevent autoimmunity and graft-vs-host rejection during transplantation therapies, 21 this similar property poses a serious threat through its diverse novel mechanisms mediating immunosuppression and cancer progression. 22 An important aspect of the action of Treg cells is via transforming growth factor (TGF) beta pathway.…”

Section: Immunosuppressive Property Of Treg Cells and Cancermentioning

confidence: 99%

<p>Regulatory T Cells in Cancer Immunotherapy: Basic Research Outcomes and Clinical Directions</p>

Zeng¹,

Jin²,

Ying³

et al. 2020

CMAR

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Cancer immunotherapy is a promising approach that has recently gained its importance in treating cancer. Despite various approaches of immunotherapies being used to target cancer cells, they are either not effective against all types of cancer or for all patients. Although efforts are being made to improve the cancer immunotherapy in all possible ways, one important hindrance that lowers the immune response to kill cancer cells is the infiltration of Regulatory T (Treg) cells into the tumor cells, favoring tumor progression, on one hand, and inhibiting the activation of T cells to respond to cancer cells, on the other hand. Therefore, new anti-cancer drugs and vaccines fail to show promising results against cancer. This is due to the infiltration of Treg cells into the tumor region and suppression of anti-cancer activity. Thus, regardless of various types of immunotherapies being practiced, understanding the mechanisms of how Treg cells favor tumor progression and inhibition of anti-cancer activity is worthwhile. Therefore, the review highlights the importance of Tregs cells and how depletion of Treg cells can pave the way to an effective immunotherapy by activating the immune responses against cancer.

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T Regulatory Cells and Priming the Suppressive Tumor Microenvironment

Cited by 173 publications

References 175 publications

KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling

KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling

Extracellular Vesicles and Tumor-Immune Escape: Biological Functions and Clinical Perspectives

<p>Regulatory T Cells in Cancer Immunotherapy: Basic Research Outcomes and Clinical Directions</p>

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