Gastric Carcinomas with Stromal B7-H3 Expression Have Lower Intratumoural CD8+ T Cell Density

Ulase, Dita; Behrens, Hans‐Michael; Krüger, Sandra; Zeißig, Sebastian; Röcken, Christoph

doi:10.3390/ijms22042129

Cited by 14 publications

(11 citation statements)

References 19 publications

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“…In contrast, in stomach cancer cell lines and xenograft models, it was revealed that B7-H3 knockdown significantly inhibited cancer invasion and metastasis capacity [ 150 ]. Mechanistically, B7-H3 + neutrophils have been found in gastric cancer tissues, which increases tumor progression and is a negative predictive marker of reduced survival [ 94 ], and a more restricted CD8 + T cell location was noted in B7-H3-high gastric cancer samples, indicating a potential immunosuppressive role of B7-H3 in gastric cancer, although no significant survival difference was observed between the B7-H3-high and B7-H3-low groups in the study [ 151 ]. Evidence for the role of B7-H3 in gastric cancer is limited and conflicting, and more studies, particularly in patients with gastric cancer, are warranted.…”

Section: B7-h3 In Different Malignanciesmentioning

confidence: 99%

Immune checkpoint of B7-H3 in cancer: from immunology to clinical immunotherapy

Zhao

Xia

et al. 2022

J Hematol Oncol

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Immunotherapy for cancer is a rapidly developing treatment that modifies the immune system and enhances the antitumor immune response. B7-H3 (CD276), a member of the B7 family that plays an immunoregulatory role in the T cell response, has been highlighted as a novel potential target for cancer immunotherapy. B7-H3 has been shown to play an inhibitory role in T cell activation and proliferation, participate in tumor immune evasion and influence both the immune response and tumor behavior through different signaling pathways. B7-H3 expression has been found to be aberrantly upregulated in many different cancer types, and an association between B7-H3 expression and poor prognosis has been established. Immunotherapy targeting B7-H3 through different approaches has been developing rapidly, and many ongoing clinical trials are exploring the safety and efficacy profiles of these therapies in cancer. In this review, we summarize the emerging research on the function and underlying pathways of B7-H3, the expression and roles of B7-H3 in different cancer types, and the advances in B7-H3-targeted therapy. Considering different tumor microenvironment characteristics and results from preclinical models to clinical practice, the research indicates that B7-H3 is a promising target for future immunotherapy, which might eventually contribute to an improvement in cancer immunotherapy that will benefit patients.

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Section: B7-h3 In Different Malignanciesmentioning

confidence: 99%

Immune checkpoint of B7-H3 in cancer: from immunology to clinical immunotherapy

Zhao

Xia

et al. 2022

J Hematol Oncol

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“…The decrease in the number and dysfunction of CD8 + T cells is one of the reasons for gastric cancer immune tolerance. In GC tissues with high expression levels of B7-H3 (CD276), the density of CD8 + T cells within the tumor was reduced, suggesting that B7-H3 may be involved in the mechanism of tumor evasion of immune responses ( 17 ). Toll-like receptor 2 (TLR2) was down-regulated in CD8 + T cells of gastric cancer patients, and TLR2 activation could increase the expression of perforin and granzyme B in CD8 + T cells and enhance CD8 + T cells cytotoxicity ( 18 ).…”

Section: The Constitution Of Gc Tmementioning

confidence: 99%

Tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer

Liu

et al. 2022

Front. Immunol.

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Tumor microenvironment is the general term for all non-cancer components and their metabolites in tumor tissue. These components include the extracellular matrix, fibroblasts, immune cells, and endothelial cells. In the early stages of tumors, the tumor microenvironment has a tumor suppressor function. As the tumor progresses, tumor immune tolerance is induced under the action of various factors, such that the tumor suppressor microenvironment is continuously transformed into a tumor-promoting microenvironment, which promotes tumor immune escape. Eventually, tumor cells manifest the characteristics of malignant proliferation, invasion, metastasis, and drug resistance. In recent years, stress effects of the extracellular matrix, metabolic and phenotypic changes of innate immune cells (such as neutrophils, mast cells), and adaptive immune cells in the tumor microenvironment have been revealed to mediate the emerging mechanisms of immune tolerance, providing us with a large number of emerging therapeutic targets to relieve tumor immune tolerance. Gastric cancer is one of the most common digestive tract malignancies worldwide, whose mortality rate remains high. According to latest guidelines, the first-line chemotherapy of advanced gastric cancer is the traditional platinum and fluorouracil therapy, while immunotherapy for gastric cancer is extremely limited, including only Human epidermal growth factor receptor 2 (HER-2) and programmed death ligand 1 (PD-L1) targeted drugs, whose benefits are limited. Clinical experiments confirmed that cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), vascular endothelial growth factor receptor (VEGFR) and other targeted drugs alone or in combination with other drugs have limited efficacy in patients with advanced gastric cancer, far less than in lung cancer, colon cancer, and other tumors. The failure of immunotherapy is mainly related to the induction of immune tolerance in the tumor microenvironment of gastric cancer. Therefore, solving the immune tolerance of tumors is key to the success of gastric cancer immunotherapy. In this study, we summarize the latest mechanisms of various components of the tumor microenvironment in gastric cancer for inducing immune tolerance and promoting the formation of the malignant phenotype of gastric cancer, as well as the research progress of targeting the tumor microenvironment to overcome immune tolerance in the treatment of gastric cancer.

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“…By immunohistochemistry and analysis of the digital image, Ulase et al demonstrated that B7-H3 is expressed chiefly in the stromal compartment of patients with GC, and CD8+ T lymphocytes are inhibited in tumors with excessive expression of B7-H3. As a result, they reported that B7-H3, as a considerable target of GC immunotherapy, can regulate cell-mediated immunity responses in patients of Western origin [ 108 ]. Accordingly, the findings of various studies demonstrated that expression of B7-H3 is increased in GC patients.…”

Section: B7-h3 (Cd276)mentioning

confidence: 99%

The Positive and Negative Immunoregulatory Role of B7 Family: Promising Novel Targets in Gastric Cancer Treatment

Bolandi

Derakhshani

Hemmat

et al. 2021

IJMS

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Gastric cancer (GC), with a heterogeneous nature, is the third leading cause of death worldwide. Over the past few decades, stable reductions in the incidence of GC have been observed. However, due to the poor response to common treatments and late diagnosis, this cancer is still considered one of the lethal cancers. Emerging methods such as immunotherapy with immune checkpoint inhibitors (ICIs) have transformed the landscape of treatment for GC patients. There are presently eleven known members of the B7 family as immune checkpoint molecules: B7-1 (CD80), B7-2 (CD86), B7-H1 (PD-L1, CD274), B7-DC (PDCD1LG2, PD-L2, CD273), B7-H2 (B7RP1, ICOS-L, CD275), B7-H3 (CD276), B7-H4 (B7x, B7S1, Vtcn1), B7-H5 (VISTA, Gi24, DD1α, Dies1 SISP1), B7-H6 (NCR3LG1), B7-H7 (HHLA2), and Ig-like domain-containing receptor 2 (ILDR2). Interaction of the B7 family of immune-regulatory ligands with the corresponding receptors resulted in the induction and inhibition of T cell responses by sending co-stimulatory and co-inhibitory signals, respectively. Manipulation of the signals provided by the B7 family has significant potential in the management of GC.

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Gastric Carcinomas with Stromal B7-H3 Expression Have Lower Intratumoural CD8+ T Cell Density

Cited by 14 publications

References 19 publications

Immune checkpoint of B7-H3 in cancer: from immunology to clinical immunotherapy

Immune checkpoint of B7-H3 in cancer: from immunology to clinical immunotherapy

Tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer

The Positive and Negative Immunoregulatory Role of B7 Family: Promising Novel Targets in Gastric Cancer Treatment

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