The distinct MHC‐unrestricted immunobiology of innate‐like and adaptive‐like human γδ T cell subsets—Nature's CAR‐T cells

Willcox, Carrie R.; Mohammed, Fiyaz; Willcox, Benjamin E.

doi:10.1111/imr.12928

Cited by 39 publications

(42 citation statements)

References 132 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Vd1 and Vg9Vd2 subtypes represent~10% and 90% of blood gd T cells, respectively (51,55,56). While polyclonal Vd1 cells are distributed throughout tissues, and exhibit adaptive-like behavior after detection of metabolic Ags and stress-induced molecules, Vd2 cells predominate in blood and exhibit innatelike behavior after detecting molecules named phosphoantigens (pAgs) and other non-peptide antigens (11,39,(57)(58)(59). A minor subtype of Vd3 cells makes up~0.2% of total circulating T cells and recognize CD1d and annexin-A2 (ANX2) (49,60).…”

Section: Untangling the Riddle Of Gd T Cell Diversitymentioning

confidence: 99%

γδ T Cells for Leukemia Immunotherapy: New and Expanding Trends

et al. 2021

View full text Add to dashboard Cite

Recently, many discoveries have elucidated the cellular and molecular diversity in the leukemic microenvironment and improved our knowledge regarding their complex nature. This has allowed the development of new therapeutic strategies against leukemia. Advances in biotechnology and the current understanding of T cell-engineering have led to new approaches in this fight, thus improving cell-mediated immune response against cancer. However, most of the investigations focus only on conventional cytotoxic cells, while ignoring the potential of unconventional T cells that until now have been little studied. γδ T cells are a unique lymphocyte subpopulation that has an extensive repertoire of tumor sensing and may have new immunotherapeutic applications in a wide range of tumors. The ability to respond regardless of human leukocyte antigen (HLA) expression, the secretion of antitumor mediators and high functional plasticity are hallmarks of γδ T cells, and are ones that make them a promising alternative in the field of cell therapy. Despite this situation, in particular cases, the leukemic microenvironment can adopt strategies to circumvent the antitumor response of these lymphocytes, causing their exhaustion or polarization to a tumor-promoting phenotype. Intervening in this crosstalk can improve their capabilities and clinical applications and can make them key components in new therapeutic antileukemic approaches. In this review, we highlight several characteristics of γδ T cells and their interactions in leukemia. Furthermore, we explore strategies for maximizing their antitumor functions, aiming to illustrate the findings destined for a better mobilization of γδ T cells against the tumor. Finally, we outline our perspectives on their therapeutic applicability and indicate outstanding issues for future basic and clinical leukemia research, in the hope of contributing to the advancement of studies on γδ T cells in cancer immunotherapy.

show abstract

Section: Untangling the Riddle Of Gd T Cell Diversitymentioning

confidence: 99%

γδ T Cells for Leukemia Immunotherapy: New and Expanding Trends

et al. 2021

View full text Add to dashboard Cite

show abstract

“…γδ T cells constitute part of the "unconventional" T-cell subset and function in unique roles, such as stress surveillance 3 . The most unique characteristics of γδ T cells are migration to peripheral tissues rather than lymphoid organs and functions independently of major histocompatibility complex (MHC)-dependent antigen presentation 4 . In mice, γδ T cells first develop in the embryonic thymus.…”

Section: Introductionmentioning

confidence: 99%

Function of γδ T cells in tumor immunology and their application to cancer therapy

2021

View full text Add to dashboard Cite

T cells of the γδ lineage are unconventional T cells with functions not restricted to MHC-mediated antigen presentation. Because of their broad antigen specificity and NK-like cytotoxicity, γδ T-cell importance in tumor immunology has been emphasized. However, some γδ T-cell subsets, especially those expressing IL-17, are immunosuppressive or tumor-promoting cells. Their cytokine profile and cytotoxicity are seemingly determined by cross-talk with microenvironment components, not by the γδTCR chain. Furthermore, much about the TCR antigen of γδ T cells remains unknown compared with the extreme diversity of their TCR chain pairs. Thus, the investigation and application of γδ T cells have been relatively difficult. Nevertheless, γδ T cells remain attractive targets for antitumor therapy because of their independence from MHC molecules. Because tumor cells have the ability to evade the immune system through MHC shedding, heterogeneous antigens, and low antigen spreading, MHC-independent γδ T cells represent good alternative targets for immunotherapy. Therefore, many approaches to using γδ T cells for antitumor therapy have been attempted, including induction of endogenous γδ T cell activation, adoptive transfer of expanded cells ex vivo, and utilization of chimeric antigen receptor (CAR)-T cells. Here, we discuss the function of γδ T cells in tumor immunology and their application to cancer therapy.

show abstract

“…T cells gamma delta, also known as γδ T cells, were characterized with the antigen specificity and NK-like cytotoxicity. γδ T cells can recognize and present tumor antigen in a major histocompatibility complex- (MHC-) independent manner, and activated γδ T cells could enhance the antitumor activity of adaptive immune cells [ 34 , 35 ]. In addition, γδ T cells also have been reported to be related to favorable prognosis [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel PPAR Signature for Predicting Prognosis, Immune Microenvironment, and Chemotherapy Response in Bladder Cancer

Zhu

Deng

et al. 2021

PPAR Research

View full text Add to dashboard Cite

Background. Mounting evidence has confirmed that peroxisome proliferator-activated receptors (PPARs) played a crucial role in the development and progression of bladder cancer (BLCA). The purpose of this study is to comprehensively investigate the function and prognostic value of PPAR-targeted genes in BLCA. Methods. The RNA sequencing data and clinical information of BLCA patients were acquired from The Cancer Genome Atlas (TCGA). The differentially expressed PPAR-targeted genes were investigated. Cox analysis and least absolute shrinkage and selection operator (LASSO) analysis were performed for screening prognostic PPAR-targeted genes and constructing the prognostic PPAR signature and then validated by GSE13507 cohort and GSE32894 cohort. A nomogram was constructed to predict the outcomes of BLCA patients in combination with PPAR signature and clinical factors. Gene set enrichment analysis (GSEA) and immune cell infiltration were implemented to explore the molecular characteristics of the signature. The Genomics of Drug Sensitivity in Cancer (GDSC) database was used to predict the chemotherapy responses of the prognostic signature. The candidate small molecule drugs targeting PPAR-targeted genes were screened by the CMAP database. Results. We constructed and validated the prognostic signature comprising of 4 PPAR-targeted genes (CPT1B, CALR, AHNAK, and FADS2), which was an independent prognostic biomarker in BLCA patients. A nomogram based on the signature and clinical factors was established in the TCGA set, and the calibration plots displayed the excellent predictive capacity. GSEA analysis indicated that PPAR signature was implicated in multiple oncogenic signaling pathways and correlated with tumor immune cell infiltration. Patients in the high-risk groups showed greater sensitivity to chemotherapy than those in the low-risk groups. Moreover, 11 candidate small molecule drugs were identified for the treatment of BLCA. Conclusion. We constructed and validated a novel PPAR signature, which showed the excellent performance in predicting prognosis and chemotherapy sensitivity of BLCA patients.

show abstract

The distinct MHC‐unrestricted immunobiology of innate‐like and adaptive‐like human γδ T cell subsets—Nature's CAR‐T cells

Cited by 39 publications

References 132 publications

γδ T Cells for Leukemia Immunotherapy: New and Expanding Trends

γδ T Cells for Leukemia Immunotherapy: New and Expanding Trends

Function of γδ T cells in tumor immunology and their application to cancer therapy

Identification of a Novel PPAR Signature for Predicting Prognosis, Immune Microenvironment, and Chemotherapy Response in Bladder Cancer

Contact Info

Product

Resources

About