Regulatory and effector functions of gamma–delta (γδ) T cells and their therapeutic potential in adoptive cellular therapy for cancer

Paul, Sourav; Lal, Girdhari

doi:10.1002/ijc.30109

Cited by 85 publications

(78 citation statements)

References 121 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although they only constitute less than 5% of all T lymphocytes, their role in the immune system should not be underestimated. γδ T cells have a wide range of functional properties including innate killing, tumor tropism, the support of DC, T cell, and NK cell functions, and, as recently demonstrated, also antigen presentation skills (64–67). Moreover, the proportion of CD56 + γδ T cells appears to be determined by their level of activation (6, 20).…”

Section: Cd56 Expression On Human Immune Cells In Health and Diseasementioning

confidence: 97%

CD56 in the Immune System: More Than a Marker for Cytotoxicity?

et al. 2017

View full text Add to dashboard Cite

Over the past years, the phenotypic and functional boundaries distinguishing the main cell subsets of the immune system have become increasingly blurred. In this respect, CD56 (also known as neural cell adhesion molecule) is a very good example. CD56 is the archetypal phenotypic marker of natural killer cells but can actually be expressed by many more immune cells, including alpha beta T cells, gamma delta T cells, dendritic cells, and monocytes. Common to all these CD56-expressing cell types are strong immunostimulatory effector functions, including T helper 1 cytokine production and an efficient cytotoxic capacity. Interestingly, both numerical and functional deficiencies and phenotypic alterations of the CD56+ immune cell fraction have been reported in patients with various infectious, autoimmune, or malignant diseases. In this review, we will discuss our current knowledge on the expression and function of CD56 in the hematopoietic system, both in health and disease.

show abstract

Section: Cd56 Expression On Human Immune Cells In Health and Diseasementioning

confidence: 97%

CD56 in the Immune System: More Than a Marker for Cytotoxicity?

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In this context, immunosuppression mediated by these factors should be considered a physiological response to damage and a drawback of a repair mechanism aimed to maintain tissue homeostasis [2,3,51]. Among the several inhibitory factors secreted by MSC, TGF-β is critical to trigger the generation of both conventional CD4 + Treg and γδ regulatory T cells [52,53]. This indicates that MSC can indeed skew the differentiation/maturation of several effector lymphocytes.…”

Section: Molecular Mechanisms Responsible For the Immunosuppressivmentioning

confidence: 99%

Mesenchymal Stromal Cells Can Regulate the Immune Response in the Tumor Microenvironment

Poggi

Giuliani

2016

Vaccines

View full text Add to dashboard Cite

The tumor microenvironment is a good target for therapy in solid tumors and hematological malignancies. Indeed, solid tumor cells’ growth and expansion can influence neighboring cells’ behavior, leading to a modulation of mesenchymal stromal cell (MSC) activities and remodeling of extracellular matrix components. This leads to an altered microenvironment, where reparative mechanisms, in the presence of sub-acute inflammation, are not able to reconstitute healthy tissue. Carcinoma cells can undergo epithelial mesenchymal transition (EMT), a key step to generate metastasis; these mesenchymal-like cells display the functional behavior of MSC. Furthermore, MSC can support the survival and growth of leukemic cells within bone marrow participating in the leukemic cell niche. Notably, MSC can inhibit the anti-tumor immune response through either carcinoma-associated fibroblasts or bone marrow stromal cells. Experimental data have indicated their relevance in regulating cytolytic effector lymphocytes of the innate and adaptive arms of the immune system. Herein, we will discuss some of the evidence in hematological malignancies and solid tumors. In particular, we will focus our attention on the means by which it is conceivable to inhibit MSC-mediated immune suppression and trigger anti-tumor innate immunity.

show abstract

“…γδ T cells are a T cell subset that comprise approximately 5–10 % of all peripheral T cells in healthy individuals [7]. Due to the antitumor function of γδ T cells, they have been proposed to have therapeutic potential for cancer treatment [8–10]. Several in vivo and in vitro data have demonstrated that γδ T cells are excellent candidates for further improving immunotherapy efficacy because of their intrinsic characteristics and function [11, 12].…”

Section: Introductionmentioning

confidence: 99%

Oligoclonal expansion of TCR Vδ T cells may be a potential immune biomarker for clinical outcome of acute myeloid leukemia

et al. 2016

View full text Add to dashboard Cite

BackgroundRecent data have shown that γδ T cells can act as mediators for immune defense against tumors. Our previous study has demonstrated that persisting clonally expanded TRDV4 T cells might be relatively beneficial for the outcome of patients with T cell acute lymphoblastic leukemia after hematopoietic stem cell transplantation (HSCT). However, little is known about the distribution and clonality of the TRDV repertoire in T cell receptor (TCR) of γδ T cells and their effects on the clinical outcome of patients with acute myeloid leukemia (AML). The aim of this study was to assess whether the oligoclonal expansion of TCR Vδ T cells could be used as an immune biomarker for AML outcome.Findingsγδ T cells were sorted from the peripheral blood of 30 patients with untreated AML and 12 healthy donors. The complementarity-determining region 3 (CDR3) sizes of eight TCR Vδ subfamily genes (TRDV1 to TRDV8) were analyzed in sorted γδ T cells using RT-PCR and GeneScan. The most frequently expressed TRDV subfamilies in the AML patients were TRDV8 (86.67 %) and TRDV2 (83.33 %), and the frequencies for TRDV1, TRDV3, TRDV4, and TRDV6 were significantly lower than those in healthy individuals. The most frequent clonally expanded TRDV subfamilies in the AML patients included TRDV8 (56.67 %) and TRDV4 (40 %). The clonal expansion frequencies of the TRDV2 and TRDV4 T cells were significantly higher than those in healthy individuals, whereas a significantly lower TRDV1 clonal expansion frequency was observed in those with AML. Moreover, the oligoclones of TRDV4 and TRDV8 were independent protective factors for complete remission. Furthermore, the oligoclonal expansion frequencies of TRDV5 and TRDV6 in patients with relapse were significantly higher than those in non-recurrent cases.ConclusionsTo the best of our knowledge, we characterized for the first time a significant alteration in the distribution and clonality of the TRDV subfamily members in γδ T cells sorted from AML patients. Clonally expanded TRDV4 and TRDV8 T cells might contribute to the immune response directed against AML, while oligoclonal TRDV5 and TRDV6 might occur in patients who undergo relapse. While the function of such γδ T cell clones requires further investigation, TRDV γδ T cell clones might be potential immune biomarkers for AML outcome.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0353-3) contains supplementary material, which is available to authorized users.

show abstract

Regulatory and effector functions of gamma–delta (γδ) T cells and their therapeutic potential in adoptive cellular therapy for cancer

Cited by 85 publications

References 121 publications

CD56 in the Immune System: More Than a Marker for Cytotoxicity?

CD56 in the Immune System: More Than a Marker for Cytotoxicity?

Mesenchymal Stromal Cells Can Regulate the Immune Response in the Tumor Microenvironment

Oligoclonal expansion of TCR Vδ T cells may be a potential immune biomarker for clinical outcome of acute myeloid leukemia

Contact Info

Product

Resources

About