Association of increased B7 protein expression by infiltrating immune cells with progression of gastric carcinogenesis

Guo, Linxin; Zhi-ju, Liu; Zhang, Yun; Quan, Qiuying; Huang, Lili; Xu, Yunyun; Cao, Liu; Zhang, Xueguang

doi:10.1097/md.0000000000014663

Cited by 20 publications

(40 citation statements)

References 45 publications

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“…In addition, we found that there was a significant correlation between B7-H3 and CD68 expression. This result is consistent with our previous findings (24), and our group also found that B7-H3 regulates the differentiation of tumor-associated macrophages in human colorectal carcinoma (43). However, the correlation between B7-H3 and CD31 or α-SMA expression was much higher than that of B7-H3 and CD68 expression, suggesting that B7-H3 may play a vital role in the tumor microenvironment, including endothelial cells and fibroblasts.…”

Section: Discussionsupporting

confidence: 93%

“…Consistent with these findings, our study indicated that patients with a higher expression of B7-H3 had significantly poorer overall survival. The expression of B7-H3 in tumor/parenchymal cells was more strongly correlated with CD8-positive and CD68positive cell infiltration and was markedly enhanced at the stages of neoplasia and GAC (24). The function of B7-H3 in promoting gastric cancer development has been studied in depth.…”

Section: Discussionmentioning

confidence: 99%

“…Immunohistochemical staining was performed according to a protocol described previously (24). Incubation with mouse antibodies against human CD31, α-SMA, CD19, CD11c, or CD68 (Ready to use; ZSGB-BIO, China); mouse anti-human Pan cytokeratin (PanCK) antibody (ab86734 1:50; Abcam, USA); or goat anti-human B7-H3 polyclonal antibody (R&D Systems, Cat# AF1027, RRID:AB_354546) was performed at 4 • C overnight, and this was followed by incubation with horseradish peroxidase (HRP)-conjugated secondary antibody (GP016029 for anti-goat or GP016129 for anti-mouse and rabbit, Genetech, China).…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Our laboratory has previously reported the expression and function of B7-H3(+)CD14(+)HLA-DR(-/low) myeloid-derived suppressor cells on human non-small-cell lung cancer (NSCLC) (23). In another study, we analyzed the trend of B7-H3 expression and its relation to CD8 as well as CD68 expression in different stages of gastric carcinogenesis (24). Furthermore, B7-H3 expression in endothelial cells and fibroblasts has been reported (9,10,25).…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of B7-H3 in α-SMA-Positive Fibroblasts Is Associated With Cancer Progression and Survival in Gastric Adenocarcinomas

et al. 2020

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Background: B7-H3 promotes tumor immune escape and is highly expressed in tumor tissues. Stromal cells in tumors, including fibroblasts, play an important role in this process; however, the role of B7-H3 in tumor fibroblasts has not been fully clarified. Methods: We examined B7-H3, CD31, and alpha-smooth muscle actin (α-SMA) protein expression in 268 gastric adenocarcinomas (GACs) by immunohistochemistry. The coexpression of B7-H3 with CD31 or α-SMA was examined using immunofluorescence double staining. Cytokine expression from fibroblasts treated with B7-H3 small interfering RNA (siRNA) was analyzed by a Quantitative reverse transcription-polymerase chain reaction (qPCR) and Enzyme-linked immunosorbent assay (ELISA). The transwell tests were conducted to assess the migration and invasion ability of fibroblasts. The overall survival was analyzed by a Kaplan-Meier analysis. Associations between categorical variables were assessed using the Pearson's Chi-square test or Fisher's exact test. Results: GAC patients with B7-H3 expression showed significantly poorer survival (P = 0.012). The overall survival of the group with high B7-H3 expression was significantly worse than the group with low B7-H3 expression in both tumor cells and in stromal cells (P = 0.007 and P = 0.048, respectively). B7-H3 expression correlated with many clinicopathological data, including tumor stage, tumor depth, lymph node involvement, and survival. Immunofluorescence staining showed that B7-H3 was expressed in tumor cells and α-SMA-positive fibroblasts. Remarkably, high expression of α-SMA was associated with a poor prognosis (P = 0.007), and the prognoses of patients with high stromal expression of B7-H3 and α-SMA were significantly worse than that of other combination types (P = 0.001). Additionally, the absence of B7-H3 led to decreased secretion of cytokines, such as interleukin (IL)-6 and vascular endothelial growth factor (VEGF), as well as a decline in migration and invasion ability in cancer-associated fibroblasts (CAFs). Zhan et al. B7-H3 Highly Expressed in CAFS Conclusions: Patients with high B7-H3 expression either in tumor cells or in stromal cells had significantly poorer overall survival. Stromal B7-H3 expression was mostly detected in α-SMA-positive CAFs. GAC patients with both stromal B7-H3-high and α-SMA-high expression had significantly poorer overall survival, suggesting that stromal B7-H3 and α-SMA expression status can serve as an indicator of poor prognosis for GAC patients.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Immunohistochemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Overexpression of B7-H3 in α-SMA-Positive Fibroblasts Is Associated With Cancer Progression and Survival in Gastric Adenocarcinomas

et al. 2020

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“…B7-H4 is a costimulatory membrane receptor expressed on APCs and cancer cells, interacting with the CD28 ligand and receptors on T lymphocytes causing an inhibitory effect. It has been associated with gastric carcinomas [137], breast cancer [138,139], non-metastatic clear cell renal cell carcinoma [140] and glioblastoma [141], among other tumor types. Its loss was also recently associated with the development of autoimmune diabetes [142].…”

Section: Immunotherapeutic Approaches Against Cancermentioning

confidence: 99%

Current Perspectives in Cancer Immunotherapy

Christofi

Baritaki

Falzone

et al. 2019

Cancers

172

121

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Different immunotherapeutic approaches have proved to be of significant clinical value to many patients with different types of advanced cancer. However, we need more precise immunotherapies and predictive biomarkers to increase the successful response rates. The advent of next generation sequencing technologies and their applications in immuno-oncology has helped us tremendously towards this aim. We are now moving towards the realization of personalized medicine, thus, significantly increasing our expectations for a more successful management of the disease. Here, we discuss the current immunotherapeutic approaches against cancer, including immune checkpoint blockade with an emphasis on anti-PD-L1 and anti-CTLA-4 monoclonal antibodies. We also analyze a growing list of other co-inhibitory and co-stimulatory markers and emphasize the mechanism of action of the principal pathway for each of these, as well as on drugs that either have been FDA-approved or are under clinical investigation. We further discuss recent advances in other immunotherapies, including cytokine therapy, adoptive cell transfer therapy and therapeutic vaccines. We finally discuss the modulation of gut microbiota composition and response to immunotherapy, as well as how tumor-intrinsic factors and immunological processes influence the mutational and epigenetic landscape of progressing tumors and response to immunotherapy but also how immunotherapeutic intervention influences the landscape of cancer neoepitopes and tumor immunoediting.

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Integrated immune gene expression signature and molecular classification in gastric cancer: New insights

Refolo¹,

Lotesoriere

Messa³

et al. 2020

Journal of Leukocyte Biology

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Gastric cancer (GC) is characterized by extreme heterogeneity due to histopathological differences, molecular characteristics, and immune gene expression signature. Until recently, several targeted therapies failed due to this complexity. The recent immunotherapy resulted in more effective and safe approaches in several malignancies. All tumors could be considered potentially immunogenic and the new knowledge regarding the interactions among tumor cells, immune cells, and tumor microenvironment (TME) allowed to reverse possible immune resistance. The immune response is a complex multisteps process that finely regulates the balance between the recognition of non-self and the prevention of autoimmunity. Cancer cells can use these pathways to suppress tumor immunity as a major mechanism of immune resistance. The recent molecular classifications of GCs by The Cancer Genome Atlas (TCGA) and by the Asian Cancer Research (ACRG) networks, together with the identification of multiple biomarkers, open new perspectives for stratification of patients who might benefit from a long-term immune checkpoint therapy. One of the major processes that contribute to an immunosuppressive microenvironment is represented by tumor angiogenesis. The cellular mechanisms inducing both angiogenesis and immunosuppressive responses are often reached by the same cell types and soluble factors, such as vascular endothelial growth factor A (VEGFA). Recent studies point out that combinatorial strategies should be adapted as useful therapeutic approach to reverse the immunosuppressive status of microenvironment occurring in a relevant percentage of gastric tumors.

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Association of increased B7 protein expression by infiltrating immune cells with progression of gastric carcinogenesis

Abstract: Supplemental Digital Content is available in the text

Cited by 20 publications

References 45 publications

Overexpression of B7-H3 in α-SMA-Positive Fibroblasts Is Associated With Cancer Progression and Survival in Gastric Adenocarcinomas

Overexpression of B7-H3 in α-SMA-Positive Fibroblasts Is Associated With Cancer Progression and Survival in Gastric Adenocarcinomas

Current Perspectives in Cancer Immunotherapy

Integrated immune gene expression signature and molecular classification in gastric cancer: New insights

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