scholarly journals The Role of Human γδ T Cells in Anti-Tumor Immunity and Their Potential for Cancer Immunotherapy

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1206 ◽  
Author(s):  
Yuxia Liu ◽  
Cai Zhang
Keyword(s):  
Innate Immunity ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cancer Immunotherapy ◽  
Immune Cells ◽  
T Cell Receptors ◽  
Γδ T Cells ◽  
Immune Defense ◽  
Cell Receptors

γδ T cells are a distinct subset of T cells whose T cell receptors consist of γ chains and δ chains, different from conventional αβ T cells. γδ T cells are considered as a member of the innate immunity because of their non-MHC restricted antigen recognition, rapid response to invading pathogens and sense early changes of malignant cells. Upon activation, they can further promote the activation of adaptive immune cells, such as T cells and B cells, by secreting various cytokines. Thus, γδ T cells are regarded as a bridge between innate immunity and acquired immunity. γδ T cells are involved in a variety of immune response processes, including immune defense and immune surveillance against infection and tumorigenesis. γδ T cells recognize multiple tumor-associated antigens or molecules in T cell receptors (TCRs)-dependent and natural killer cell receptors (NKRs)-dependent ways. γδ T cells not only display a direct killing capacity on a variety of tumors, but also exert anti-tumor immune responses indirectly by facilitating the function of other immune cells, such as dendritic cells (DCs), B cells and CD8+ T cells. In this review, we summarize the major subpopulations, the tumor recognition mechanisms, and the anti-tumor effects of human γδ T cells, particularly the potential of γδ T cells for cancer immunotherapy.

scholarly journals Antibody-mediated B-cell depletion before adoptive immunotherapy with T cells expressing CD20-specific chimeric T-cell receptors facilitates eradication of leukemia in immunocompetent mice

Blood ◽  
2009 ◽  
Vol 114 (27) ◽  
pp. 5454-5463 ◽  
Author(s):  
Scott E. James ◽  
Nural N. Orgun ◽  
Thomas F. Tedder ◽  
Mark J. Shlomchik ◽  
Michael C. Jensen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Transgenic Mice ◽  
B Cell ◽  
T Cell Receptors ◽  
Adoptive T Cell Therapy ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Cell Receptors

Abstract We have established a model of leukemia immunotherapy using T cells expressing chimeric T-cell receptors (cTCRs) targeting the CD20 molecule expressed on normal and neoplastic B cells. After transfer into human CD20 (hCD20) transgenic mice, cTCR+ T cells showed antigen-specific delayed egress from the lungs, concomitant with T-cell deletion. Few cTCR+ T cells reached the bone marrow (BM) in hCD20 transgenic mice, precluding effectiveness against leukemia. Anti-hCD20 antibody-mediated B-cell depletion before adoptive T-cell therapy permitted egress of mouse CD20-specific cTCR+ T cells from the lungs, enhanced T-cell survival, and promoted cTCR+ T cell–dependent elimination of established mouse CD20+ leukemia. Furthermore, CD20-specific cTCR+ T cells eliminated residual B cells refractory to depletion with monoclonal antibodies. These findings suggest that combination of antibody therapy that depletes antigen-expressing normal tissues with adoptive T-cell immunotherapy enhances the ability of cTCR+ T cells to survive and control tumors.

A blend of broadly-reactive and pathogen-selected Vγ4 Vδ1 T cell receptors confer broad bacterial reactivity of resident memory γδ T cells

2021 ◽  
Author(s):  
Camille Khairallah ◽  
Julie A. Bettke ◽  
Oleksandr Gorbatsevych ◽  
Zhijuan Qiu ◽  
Yue Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptors ◽  
Γδ T Cells ◽  
Cell Receptors

Clonal expansion of γδ T cells expressing two distinct T‐cell receptors

1996 ◽  
Vol 94 (1) ◽  
pp. 62-64 ◽  
Author(s):  
Thomas Hinz ◽  
Sibylle Marx ◽  
Christoph Nerl ◽  
Dieter Kabelitz
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptors ◽  
Γδ T Cells ◽  
Clonal Expansion ◽  
Cell Receptors

A class of γδ T cell receptors recognize the underside of the antigen-presenting molecule MR1

Science ◽  
2019 ◽  
Vol 366 (6472) ◽  
pp. 1522-1527 ◽  
Author(s):  
Jérôme Le Nours ◽  
Nicholas A. Gherardin ◽  
Sri H. Ramarathinam ◽  
Wael Awad ◽  
Florian Wiede ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptors ◽  
Γδ T Cells ◽  
Mhc I ◽  
Cell Receptors ◽  
Histocompatibility Complex ◽  
Antigen Complex ◽  
Binding Cleft ◽  
Antigen Presenting

T cell receptors (TCRs) recognize antigens presented by major histocompatibility complex (MHC) and MHC class I–like molecules. We describe a diverse population of human γδ T cells isolated from peripheral blood and tissues that exhibit autoreactivity to the monomorphic MHC-related protein 1 (MR1). The crystal structure of a γδTCR–MR1–antigen complex starkly contrasts with all other TCR–MHC and TCR–MHC-I-like complex structures. Namely, the γδTCR binds underneath the MR1 antigen-binding cleft, where contacts are dominated by the MR1 α3 domain. A similar pattern of reactivity was observed for diverse MR1-restricted γδTCRs from multiple individuals. Accordingly, we simultaneously report MR1 as a ligand for human γδ T cells and redefine the parameters for TCR recognition.

scholarly journals Retracted:Antitumor activity of human γδ T cells transducted with CD8 and with T-cell receptors of tumor-specific cytotoxic T lymphocytes

2012 ◽  
Vol 103 (8) ◽  
pp. 1414-1419 ◽  
Author(s):  
Takeshi Hanagiri ◽  
Yoshiki Shigematsu ◽  
Koji Kuroda ◽  
Tetsuro Baba ◽  
Hironobu Shiota ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
T Cell Receptors ◽  
Γδ T Cells ◽  
Cell Receptors

scholarly journals Innate Immune Cells and Their Contribution to T-Cell-Based Immunotherapy

2020 ◽  
Vol 21 (12) ◽  
pp. 4441 ◽  
Author(s):  
Pierpaolo Ginefra ◽  
Girieca Lorusso ◽  
Nicola Vannini
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cancer Immunotherapy ◽  
Cancer Patients ◽  
Immune Cells ◽  
Adoptive Cell Therapy ◽  
Adaptive Immune Response ◽  
Immune Checkpoint Blockade ◽  
Innate Immune ◽  
Innate Immune Cells

In recent years, immunotherapy has become the most promising therapy for a variety of cancer types. The development of immune checkpoint blockade (ICB) therapies, the adoptive transfer of tumor-specific T cells (adoptive cell therapy (ACT)) or the generation of T cells engineered with chimeric antigen receptors (CAR) have been successfully applied to elicit durable immunological responses in cancer patients. However, not all the patients respond to these therapies, leaving a consistent gap of therapeutic improvement that still needs to be filled. The innate immune components of the tumor microenvironment play a pivotal role in the activation and modulation of the adaptive immune response against the tumor. Indeed, several efforts are made to develop strategies aimed to harness innate immune cells in the context of cancer immunotherapy. In this review, we describe the contribution of innate immune cells in T-cell-based cancer immunotherapy and the therapeutic approaches implemented to broaden the efficacy of these therapies in cancer patients.

scholarly journals Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers

Nature ◽  
2021 ◽  
Author(s):  
Justina X. Caushi ◽  
Jiajia Zhang ◽  
Zhicheng Ji ◽  
Ajay Vaghasia ◽  
Boyang Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
T Cell Receptors ◽  
Tumour Microenvironment ◽  
Lung Cancers ◽  
Cell Receptors ◽  
Interleukin 7

AbstractPD-1 blockade unleashes CD8 T cells1, including those specific for mutation-associated neoantigens (MANA), but factors in the tumour microenvironment can inhibit these T cell responses. Single-cell transcriptomics have revealed global T cell dysfunction programs in tumour-infiltrating lymphocytes (TIL). However, the majority of TIL do not recognize tumour antigens2, and little is known about transcriptional programs of MANA-specific TIL. Here, we identify MANA-specific T cell clones using the MANA functional expansion of specific T cells assay3 in neoadjuvant anti-PD-1-treated non-small cell lung cancers (NSCLC). We use their T cell receptors as a ‘barcode’ to track and analyse their transcriptional programs in the tumour microenvironment using coupled single-cell RNA sequencing and T cell receptor sequencing. We find both MANA- and virus-specific clones in TIL, regardless of response, and MANA-, influenza- and Epstein–Barr virus-specific TIL each have unique transcriptional programs. Despite exposure to cognate antigen, MANA-specific TIL express an incompletely activated cytolytic program. MANA-specific CD8 T cells have hallmark transcriptional programs of tissue-resident memory (TRM) cells, but low levels of interleukin-7 receptor (IL-7R) and are functionally less responsive to interleukin-7 (IL-7) compared with influenza-specific TRM cells. Compared with those from responding tumours, MANA-specific clones from non-responding tumours express T cell receptors with markedly lower ligand-dependent signalling, are largely confined to HOBIThigh TRM subsets, and coordinately upregulate checkpoints, killer inhibitory receptors and inhibitors of T cell activation. These findings provide important insights for overcoming resistance to PD-1 blockade.

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