α-GalCer and iNKT Cell-Based Cancer Immunotherapy: Realizing the Therapeutic Potentials

Zhang, Yingting; Springfield, Ryan; Chen, Siyang; Li, Xin; Feng, Xiaotian; Moshirian, Rosa; Yang, Rongliang; Yuan, Weiming

doi:10.3389/fimmu.2019.01126

Cited by 55 publications

(43 citation statements)

References 74 publications

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“…α-GalCer is by far the most explored structure and the C-glycoside analog 7DW8-5 with an aryl side chain were also attractive structures for immune studies. Many excellent reviews about α-GalCer and its analogs have been published (Carreño et al, 2014;Marzabadi and Franck, 2017;Waldowska et al, 2017;Zhang et al, 2019).…”

Section: α-Galactosylceramide (α-Galcer)mentioning

confidence: 99%

“…α-GalCer has been applied as an adjuvant in many studies (Mattarollo and Smyth, 2013;Faveeuw and Trottein, 2014;Artiaga et al, 2016;Liu and Guo, 2017;Fujii et al, 2018;Sainz et al, 2018;Yamashita et al, 2018;Zhang et al, 2019), including vaccines against cancer, influenza, and malaria. To improve the delivery efficiency of α-GalCer and therefore enhancing the activation of iNKT cells, various delivery systems have been designed, such as liposomes, poly(lactic-co-glycolic acid) (PLGA) particles and bacteriophage particles (Macho-Fernandez et al, 2014;Dölen et al, 2016;Ghinnagow et al, 2017a,b;Sartorius et al, 2018).…”

Section: α-Galactosylceramide (α-Galcer)mentioning

confidence: 99%

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Carbohydrate Conjugates in Vaccine Developments

Lang

Huang

2020

Front. Chem.

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Vaccines are powerful tools that can activate the immune system for protection against various diseases. As carbohydrates can play important roles in immune recognition, they have been widely applied in vaccine development. Carbohydrate antigens have been investigated in vaccines against various pathogenic microbes and cancer. Polysaccharides such as dextran and β-glucan can serve as smart vaccine carriers for efficient antigen delivery to immune cells. Some glycolipids, such as galactosylceramide and monophosphoryl lipid A, are strong immune stimulators, which have been studied as vaccine adjuvants. In this review, we focus on the current advances in applying carbohydrates as vaccine delivery carriers and adjuvants. We will discuss the examples that involve chemical modifications of the carbohydrates for effective antigen delivery, as well as covalent antigen-carbohydrate conjugates for enhanced immune responses.

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Section: α-Galactosylceramide (α-Galcer)mentioning

confidence: 99%

Section: α-Galactosylceramide (α-Galcer)mentioning

confidence: 99%

Carbohydrate Conjugates in Vaccine Developments

Lang

Huang

2020

Front. Chem.

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“…Therefore, the more antigen-specific T cells that enter the TME, the greater chance they may terminally differentiate into exhausted T cells. For NKT cell, although it is an innate-like lymphocyte with invariant TCR that exerts potent antitumor immunity ( 55 ), the activation and expansion of NKT cells requires the presentation of α-galactosylceramide (α-GalCer) ( 56 ), a specific glycolipid antigen that is almost absent in the TME, and thus the expansion capacity of NKT cells in the TME is restrained. Therefore, compared to other T cell subsets that proliferate rapidly in the TME in the γδT-hi group, including CD8+ T cells, CD4+ T cells or γδ T cells, the number of NKT cells remains unchanged, resulting in the relatively lower proportions compared to the γδT-lo group.…”

Section: Discussionmentioning

confidence: 99%

High Abundance of Intratumoral γδ T Cells Favors a Better Prognosis in Head and Neck Squamous Cell Carcinoma: A Bioinformatic Analysis

Wei

Guo

et al. 2020

Front. Immunol.

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γδ T cells are a small subset of unconventional T cells that are enriched in the mucosal areas, and are responsible for pathogen clearance and maintaining integrity. However, the role of γδ T cells in head and neck squamous cell carcinoma (HNSCC) is largely unknown. Here, by using RNA-seq data from The Cancer Genome Atlas (TCGA), we discovered that HNSCC patients with higher levels of γδ T cells were positively associated with lower clinical stages and better overall survival, and high abundance of γδ T cells was positively correlated with CD8+/CD4+ T cell infiltration. Gene ontology and pathway analyses showed that genes associated with T cell activation, proliferation, effector functions, cytotoxicity, and chemokine production were enriched in the group with a higher γδ T cell abundance. Furthermore, we found that the abundance of γδ T cells was positively associated with the expression of the butyrophilin (BTN) family proteins BTN3A1/BTN3A2/BTN3A3 and BTN2A1, but only MICB, one of the ligands of NKG2D, was involved in the activation of γδ T cells, indicating that the BTN family proteins might be involved in the activation and proliferation of γδ T cells in the tumor microenvironment of HNSCC. Our results indicated that γδ T cells, along with their ligands, are promising targets in HNSCC with great prognostic values and treatment potentials.

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“…Altogether, these cells are promising tools for potential use as HDT in human TB, in a similar way to their use in cancer immunotherapy (36).…”

Section: Diverse Nkt Cellsmentioning

confidence: 94%

Harnessing Unconventional T Cells for Immunotherapy of Tuberculosis

et al. 2020

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Even if the incidence of tuberculosis (TB) has been decreasing over the last years, the number of patients with TB is increasing worldwide. The emergence of multidrugresistant and extensively drug-resistant TB is making control of TB more difficult. Mycobacterium bovis bacillus Calmette-Guérin vaccine fails to prevent pulmonary TB in adults, and there is an urgent need for a vaccine that is also effective in patients with human immunodeficiency virus (HIV) coinfection. Therefore, TB control may benefit on novel therapeutic options beyond antimicrobial treatment. Host-directed immunotherapies could offer therapeutic strategies for patients with drug-resistant TB or with HIV and TB coinfection. In the last years, the use of donor lymphocytes after hematopoietic stem cell transplantation has emerged as a new strategy in the cure of hematologic malignancies in order to induce graft-versus leukemia and graft-versusinfection effects. Moreover, adoptive therapy has proven to be effective in controlling cytomegalovirus and Epstein-Barr virus reactivation in immunocompromised patients with ex vivo expanded viral antigen-specific T cells. Unconventional T cells are a heterogeneous group of T lymphocytes with limited diversity. One of their characteristics is that antigen recognition is not restricted by the classical major histocompatibility complex (MHC). They include CD1 (cluster of differentiation 1)-restricted T cells, MHCrelated protein-1-restricted mucosal-associated invariant T (MAIT) cells, MHC class Ib-reactive T cells, and γδ T cells. Because these T cells are genotype-independent, they are also termed "donor unrestricted" T cells. The combined features of low donor diversity and the lack of genetic restriction make these cells suitable candidates for T cell-based immunotherapy of TB.

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α-GalCer and iNKT Cell-Based Cancer Immunotherapy: Realizing the Therapeutic Potentials

Cited by 55 publications

References 74 publications

Carbohydrate Conjugates in Vaccine Developments

Carbohydrate Conjugates in Vaccine Developments

High Abundance of Intratumoral γδ T Cells Favors a Better Prognosis in Head and Neck Squamous Cell Carcinoma: A Bioinformatic Analysis

Harnessing Unconventional T Cells for Immunotherapy of Tuberculosis

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