<i>In situ</i>expression and significance of B7 costimulatory molecules within tissues of human gastric carcinoma

Chen, Xiaoli; Cao, Xudong; Kang, An-Jing; Wang, Kang-Min; Su, Bin; Wang, Yili

doi:10.3748/wjg.v9.i6.1370

Cited by 26 publications

(26 citation statements)

References 34 publications

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“…We also examined expression of B7h, which is a ligand for ICOS, but no obvious expression in surgically resected specimens of non-small cell lung cancer was noted (data not shown). Expression of two other B7 family members, B7.1 and B7.2, is undetectable or low in most tumor cells (23)(24)(25). Thus, expression of B7 family members differs among tumor tissues.…”

Section: Discussionmentioning

confidence: 98%

B7-H1 Expression on Non-Small Cell Lung Cancer Cells and Its Relationship with Tumor-Infiltrating Lymphocytes and Their PD-1 Expression

Konishi

Yamazaki²,

Azuma³

et al. 2004

Clinical Cancer Research

619

424

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Purpose: B7-H1/PD-L1 (B7-H1) and B7-DC/PD-L2 (B7-DC) are ligands for the receptor PD-1, which is known to negatively regulate T-cell activation. In the present study, we investigated the expression of B7-H1 and B7-DC in tumor specimens of non-small cell lung cancer and their relationships with clinicopathological variables and postoperative survival. Furthermore, we examined the correlation between B7-H1 expression on tumor cells and the number of tumor-infiltrating lymphocytes (TILs) or PD-1 expression on TILs.Experimental Design: The expression of B7-H1 and B7-DC in 52 surgically resected specimens of non-small cell lung cancer was evaluated immunohistochemically.Results: Expression of B7-H1 and B7-DC was focally observed in all non-small cell lung cancer tumor specimens. No relationship was found between the expression of B7-H1 or B7-DC and clinicopathological variables or postoperative survival. However, in the same sections evaluated, significantly fewer TILs were identified in B7-H1-positive tumor regions than in B7-H1-negative tumor regions in a subset of five patients (P ‫؍‬ 0.01). Moreover, the percentage of TILs expressing PD-1 was significantly lower in B7-H1-positive tumor regions than in B7-H1-negative tumor regions (P ‫؍‬ 0.02).Conclusions: The expression of B7-H1 on tumor cells in local areas reciprocally correlated with the number of TILs, and this may contribute to negative regulation in antitumor immune responses in non-small cell lung cancer.

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Section: Discussionmentioning

confidence: 98%

B7-H1 Expression on Non-Small Cell Lung Cancer Cells and Its Relationship with Tumor-Infiltrating Lymphocytes and Their PD-1 Expression

Konishi

Yamazaki²,

Azuma³

et al. 2004

Clinical Cancer Research

619

424

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show abstract

“…[32][33][34][35][36] Importantly, emerging evidence demonstrated that EBV is present in a considerable amount of tumor cells of gastric cancer patients worldwide. Studies confirmed that EBV-positive gastric cancer cell line (AGS-EBV) was resistant to the chemotherapy drugs docetaxel and 5-fluorouracil as compared with EBV-negative cells (AGS).…”

Section: E1249558-10mentioning

confidence: 99%

CRISPR-Cas9-mediated disruption of PD-1 on human T cells for adoptive cellular therapies of EBV positive gastric cancer

Zou

Chen

et al. 2016

OncoImmunology

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The successful use of immune cell checkpoint inhibitors PD-1 and PD-L1, over the past 5 y has raised the concern of using immunotherapy to treat various cancers. Epstein-Barr virus-associated gastric cancer (EBVaGC) exhibits high infiltration of lymphocytes and high amplification of immune-related genes including PD-L1 as distinguished from Epstein-Barr virus-non-associated gastric cancer (EBVnGC). Here, we presume that this PD-1/PD-L1 pathway may hinder the efficacy of adoptive T cell therapy toward EBVaGC. These studies reveal possibility of generating PD-1-disrupted CTL by CRISPR-Cas9 system and demonstrate enhanced immune response of these PD-1-disrupted CTLs to the EBV-LMP2A antigen and superior cytotoxicity to the EBV-positive gastric cancer cell. In addition, when combined with low-dose radiotherapy, these PD-1-disrupted CTLs mediated an impressive antitumor effect in a xenograft mouse model of EBVaGC. Taken together, these studies illustrate PD-1/PD-L1-mediated immune tolerance of EBVaGC and provide a new strategy for targeting immune checkpoints to break the tolerance for the T cell-based adoptive therapy.

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“…B7-H1 forms and maintains an immunosuppressive microenvironment by inhibiting the proliferation of activated T cells and inducing the apoptosis of T cells [4]. B7-H1 is over-expressed in tumor cells compared with normal gastric epithelial cells [5–7]. Increased B7-H1 expression has also been detected in human gastric epithelial cells in cases of Helicobacter pylori (HP) infection [8].…”

Section: Introductionmentioning

confidence: 99%

Helicobacter Pylori Promote B7-H1 Expression by Suppressing miR-152 and miR-200b in Gastric Cancer Cells

Xie

et al. 2017

PLoS ONE

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The most common cause of gastric cancer is infection with helicobacter pylori (HP), but the associated molecular mechanism is not well understood. In the present study, we found a marked increase in the expression of B7-H1, a member of the B7 co-stimulatory family of molecules that bind to programmed death-1 (PD-1) and play a critical immunoregulatory role in the cell-mediated immune response, in HP-positive gastric cancer tissue. Infection of cultured gastric cancer cells with HP promoted B7-H1 expression and inhibited miR-152 and miR-200b expression. We further demonstrated that these two miRNAs targeted B7-H1 mRNA and suppressed B7-H1 expression in gastric cancer cells. Finally, B7-H1 expression was found to correlate with miR-152 and miR-200b levels in gastric tumor tissues from human patients. Our findings suggest a novel mechanism by which HP infection promotes gastric cancer and also suggest potential targets, i.e., miR-152 and miR-200b, for the prevention and treatment of gastric cancer.

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In situexpression and significance of B7 costimulatory molecules within tissues of human gastric carcinoma

Cited by 26 publications

References 34 publications

B7-H1 Expression on Non-Small Cell Lung Cancer Cells and Its Relationship with Tumor-Infiltrating Lymphocytes and Their PD-1 Expression

B7-H1 Expression on Non-Small Cell Lung Cancer Cells and Its Relationship with Tumor-Infiltrating Lymphocytes and Their PD-1 Expression

CRISPR-Cas9-mediated disruption of PD-1 on human T cells for adoptive cellular therapies of EBV positive gastric cancer

Helicobacter Pylori Promote B7-H1 Expression by Suppressing miR-152 and miR-200b in Gastric Cancer Cells

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