European Patent in Immunoncology: From Immunological Principles of Implantation to Cancer Treatment

Würfel, Franziska; Winterhalter, Christoph; Trenkwalder, Peter; Wirtz, Ralph M.; Würfel, W.

doi:10.3390/ijms20081830

Cited by 12 publications

(10 citation statements)

References 237 publications

(354 reference statements)

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“…Taking advantage of the early studies on fetal-maternal immune tolerance, HLA-G-mediated immune inhibition has been well-acknowledged in the broader spectrum of health and disease situations. HLA-G expression favors the acceptance of allograft organ transplantation, whereas it provides an additional strategy for cancer cells to escape from immune surveillance and clearance ( 89 , 90 ). HLA-G/ILTs engagement activates the phosphorylation of the ITIMs contained in the tyrosine residues, which present docking sites for Src homology 2 (SH2) protein tyrosine phosphates SHP-1 and SHP-2, thus initiating an inhibitory signaling cascade.…”

Section: Hla-g/ilts Bindingmentioning

confidence: 99%

HLA-G/ILTs Targeted Solid Cancer Immunotherapy: Opportunities and Challenges

Lin

Yan

2021

Front. Immunol.

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Immune checkpoint inhibitors (ICIs) have become a promising immunotherapy for cancers. Human leukocyte antigen-G (HLA-G), a neoantigen, its biological functions and clinical relevance have been extensively investigated in malignancies, and early clinical trials with “anti-HLA-G strategy” are being launched for advance solid cancer immunotherapy. The mechanism of HLA-G as a new ICI is that HLA-G can bind immune cell bearing inhibitory receptors, the immunoglobulin-like transcript (ILT)-2 and ILT-4. HLA-G/ILT-2/-4 (HLA-G/ILTs) signaling can drive comprehensive immune suppression, promote tumor growth and disease progression. Though clinical benefits could be expected with application of HLA-G antibodies to blockade the HLA-G/ILTs signaling in solid cancer immunotherapy, major challenges with the diversity of HLA-G isoforms, HLA-G/ILTs binding specificity, intra- and inter-tumor heterogeneity of HLA-G, lack of isoform-specific antibodies and validated assay protocols, which could dramatically affect the clinical efficacy. Clinical benefits of HLA-G-targeted solid cancer immunotherapy may be fluctuated or even premature unless major challenges are addressed.

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Section: Hla-g/ilts Bindingmentioning

confidence: 99%

HLA-G/ILTs Targeted Solid Cancer Immunotherapy: Opportunities and Challenges

Lin

Yan

2021

Front. Immunol.

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“…HLA-G induced immune suppression has been extensively documented (including direct and/or indirect as well as long- and short-term), and the immunosuppressive functions of HLA-G have been well established ( 29 , 35 ). The signalling between HLA-G and receptors KIR2DL4, ILT-2, ILT-4, CD8, and CD160 expressed on different types of immune cells is a fundamental prerequisite for the aforementioned immune suppressive functions of HLA-G ( 36 ). Recently, the immune inhibitory NKG2A/CD94 receptor, a well-known receptor for HLA-E, has been reported to be a new HLA-G allele-dependent receptor ( 37 ).…”

Section: Immune Modulation Of Hla-g Moleculementioning

confidence: 99%

Perspective of HLA-G Induced Immunosuppression in SARS-CoV-2 Infection

Lin

Yan

2021

Front. Immunol.

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COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has threatened public health worldwide. Host antiviral immune responses are essential for viral clearance and disease control, however, remarkably decreased immune cell numbers and exhaustion of host cellular immune responses are commonly observed in patients with COVID-19. This is of concern as it is closely associated with disease severity and poor outcomes. Human leukocyte antigen-G (HLA-G) is a ligand for multiple immune inhibitory receptors, whose expression can be upregulated by viral infections. HLA-G/receptor signalling, such as engagement with immunoglobulin-like transcript 2 (ILT-2) or ILT-4, not only inhibit T and natural killer (NK) cell immune responses, dendritic cell (DC) maturation, and B cell antibody production. It also induces regulatory cells such as myeloid-derived suppressive cells (MDSCs), or M2 type macrophages. Moreover, HLA-G interaction with CD8 and killer inhibitory receptor (KIR) 2DL4 can provoke T cell apoptosis and NK cell senescence. In this context, HLA-G can induce profound immune suppression, which favours the escape of SARS-CoV-2 from immune attack. Although detailed knowledge on the clinical relevance of HLA-G in SARS-CoV-2 infection is limited, we herein review the immunopathological aspects of HLA-G/receptor signalling in SARS-CoV-2 infection, which could provide a better understanding of COVID-19 disease progression and identify potential immunointerventions to counteract SARS-CoV-2 infection.

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“…Cancer immunotherapy is aimed at improving the immune system's ability to eliminate cancer cells. Several types of immunotherapies have been developed to improve the immune system [ 7 , 8 ]. Early immunotherapy is mainly focused on activating nonspecific immune cells such as NK cells and dendritic cells by cytokine stimulation [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Immune Cell Landscape in Gastric Cancer

Yang

Wang

et al. 2021

BioMed Research International

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Background. The tumor-infiltrating immune cells are closely associated with the prognosis of gastric cancer (GC). This article is aimed at determining the composition change of immune cells and immune regulatory factors in GC and normal tissues, depicting their prognosis value in GC, and revealing the relationship between them and GC clinical parameters. Methods. We used CIBERSORT to calculate the proportion of 22 immune cells in the GC or normal tissues; a t -test was applied to assess the expression difference of immune cells and immune regulatory factors in normal and GC tissues. The relationship of the immune cells, immune regulatory factors, and GC patients’ clinical characteristics was assessed by univariate analysis. Results. In this study, we found that the proportion of macrophages increased, while plasma cells and monocytes decreased in GC tissues. In these immune fractions, Tregs and naïve B cells were found to be correlated with GC patients’ prognosis. Interestingly, the expression of immune regulatory factors was ambiguous with their classical function in GC tissues. For example, TIM-3, FOXP3, and CMTM6 were overexpressed, while CD27 and PD-1 were underexpressed in GC tissues. We also found that IDO1, PD-1, TIGIT, and TIM-3 were highly expressed in high-grade GC tissues, the HERC2 expression level was related to patients’ gender, and the TIGIT expression level was sensitive to targeted therapy. Furthermore, our results suggested that the infiltration of Tregs and naive B cells was strongly correlated with the T stage, radiation therapy, targeted molecular therapy, and the expression levels of TIM-3 and FOXP3 in GC. Conclusion. The expression pattern of tumor-infiltrating immune cells and immune regulatory factors was systematically depicted in the GC tumor microenvironment, indicating that individualized treatment based on the tumor-infiltrating immune cells and immune regulatory factors may be beneficial to GC patients.

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European Patent in Immunoncology: From Immunological Principles of Implantation to Cancer Treatment

Cited by 12 publications

References 237 publications

HLA-G/ILTs Targeted Solid Cancer Immunotherapy: Opportunities and Challenges

HLA-G/ILTs Targeted Solid Cancer Immunotherapy: Opportunities and Challenges

Perspective of HLA-G Induced Immunosuppression in SARS-CoV-2 Infection

Immune Cell Landscape in Gastric Cancer

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