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Epstein-Barr Virus-Associated Gastric Carcinoma and Specific Features of the Accompanying Immune Response.

Cho J, Kang MS, Kim KM - J Gastric Cancer (2016)

Bottom Line: In EBVaGC, deregulation of the expression of immune response-related genes promotes marked intra- or peritumoral immune cell infiltration.The expression of programmed death receptor-ligand 1 is known to be increased in EBVaGC, and therefore, it has been proposed as a favorable prognostic factor for patients with EBVaGC, albeit some data supporting this claim are controversial.Therefore, further research is necessary to better understand the role of tumor microenvironment in EBVaGC.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology & Translational Genomics, Samsung Medical Center, Seoul, Korea.

ABSTRACT
Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is one of the four subtypes of gastric carcinoma (GC), as defined by the novel classification recently proposed by The Cancer Genome Atlas. EBVaGC has several clinicopathological features such as longer survival and higher frequency of lymphoepithelioma-like carcinoma (LELC) and carcinoma with Crohn's disease-like lymphoid reaction that distinguish it from EBV-negative GC. The intensity and pattern of host cellular immune response in GC have been found to significantly correlate with the prognosis of patients with GC, suggesting that immune reaction and tumor microenvironment have critical roles in the progression of GC, and in particular, EBVaGC. Here, we reviewed the cellular and molecular mechanisms underlying prominent immune reactions in patients with EBVaGC. In EBVaGC, deregulation of the expression of immune response-related genes promotes marked intra- or peritumoral immune cell infiltration. The expression of programmed death receptor-ligand 1 is known to be increased in EBVaGC, and therefore, it has been proposed as a favorable prognostic factor for patients with EBVaGC, albeit some data supporting this claim are controversial. Overall, the underlying mechanisms and clinical significance of the host cellular immune response in patients with EBVaGC have not been thoroughly elucidated. Therefore, further research is necessary to better understand the role of tumor microenvironment in EBVaGC.

No MeSH data available.


Related in: MedlinePlus

Photomicrographs of CD4- (A), CD8- (B), CD20- (C), and CD1a- (D) positive immune cells around Epstein-Barr virus-positive carcinoma cells (magnification: A~C, ×40).
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Figure 2: Photomicrographs of CD4- (A), CD8- (B), CD20- (C), and CD1a- (D) positive immune cells around Epstein-Barr virus-positive carcinoma cells (magnification: A~C, ×40).

Mentions: At the genomic level, EBVaGC is accompanied by a relatively frequent recurrent amplification of the 9p24.1 locus containing the CD274 gene encoding PD-L1, which is also known as B7-H1.18 PD-L1 expression on tumor cells is known to play an important role in immune evasion. This is accomplished through the interaction with the co-inhibitory molecule programmed death receptor-1 (PD-1) expressed by T cells.39 The PD-1/PD-L1 interaction inhibits T lymphocyte proliferation, survival, and effector functions such as cytotoxicity and cytokine release. In addition, it induces apoptosis of tumor-specific T cells, promotes the differentiation of CD4+ T cells into Foxp3+ regulatory T (Treg) cells, and increases the resistance of tumor cells to cytotoxic T lymphocyte attacks.40 This interaction mediates the suppression of T cell functions, and thus reduces T-cell receptor (TCR)-mediated proliferation and cytokine production.39 Actually, we observed markedly increased levels of CD4- and CD8-positive T cells and a moderate increase of CD20 positive B cells around EBV-positive tumor cells. However, we observed very small numbers of CD1a positive dendritic cells (Fig. 2).


Epstein-Barr Virus-Associated Gastric Carcinoma and Specific Features of the Accompanying Immune Response.

Cho J, Kang MS, Kim KM - J Gastric Cancer (2016)

Photomicrographs of CD4- (A), CD8- (B), CD20- (C), and CD1a- (D) positive immune cells around Epstein-Barr virus-positive carcinoma cells (magnification: A~C, ×40).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834615&req=5

Figure 2: Photomicrographs of CD4- (A), CD8- (B), CD20- (C), and CD1a- (D) positive immune cells around Epstein-Barr virus-positive carcinoma cells (magnification: A~C, ×40).
Mentions: At the genomic level, EBVaGC is accompanied by a relatively frequent recurrent amplification of the 9p24.1 locus containing the CD274 gene encoding PD-L1, which is also known as B7-H1.18 PD-L1 expression on tumor cells is known to play an important role in immune evasion. This is accomplished through the interaction with the co-inhibitory molecule programmed death receptor-1 (PD-1) expressed by T cells.39 The PD-1/PD-L1 interaction inhibits T lymphocyte proliferation, survival, and effector functions such as cytotoxicity and cytokine release. In addition, it induces apoptosis of tumor-specific T cells, promotes the differentiation of CD4+ T cells into Foxp3+ regulatory T (Treg) cells, and increases the resistance of tumor cells to cytotoxic T lymphocyte attacks.40 This interaction mediates the suppression of T cell functions, and thus reduces T-cell receptor (TCR)-mediated proliferation and cytokine production.39 Actually, we observed markedly increased levels of CD4- and CD8-positive T cells and a moderate increase of CD20 positive B cells around EBV-positive tumor cells. However, we observed very small numbers of CD1a positive dendritic cells (Fig. 2).

Bottom Line: In EBVaGC, deregulation of the expression of immune response-related genes promotes marked intra- or peritumoral immune cell infiltration.The expression of programmed death receptor-ligand 1 is known to be increased in EBVaGC, and therefore, it has been proposed as a favorable prognostic factor for patients with EBVaGC, albeit some data supporting this claim are controversial.Therefore, further research is necessary to better understand the role of tumor microenvironment in EBVaGC.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology & Translational Genomics, Samsung Medical Center, Seoul, Korea.

ABSTRACT
Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is one of the four subtypes of gastric carcinoma (GC), as defined by the novel classification recently proposed by The Cancer Genome Atlas. EBVaGC has several clinicopathological features such as longer survival and higher frequency of lymphoepithelioma-like carcinoma (LELC) and carcinoma with Crohn's disease-like lymphoid reaction that distinguish it from EBV-negative GC. The intensity and pattern of host cellular immune response in GC have been found to significantly correlate with the prognosis of patients with GC, suggesting that immune reaction and tumor microenvironment have critical roles in the progression of GC, and in particular, EBVaGC. Here, we reviewed the cellular and molecular mechanisms underlying prominent immune reactions in patients with EBVaGC. In EBVaGC, deregulation of the expression of immune response-related genes promotes marked intra- or peritumoral immune cell infiltration. The expression of programmed death receptor-ligand 1 is known to be increased in EBVaGC, and therefore, it has been proposed as a favorable prognostic factor for patients with EBVaGC, albeit some data supporting this claim are controversial. Overall, the underlying mechanisms and clinical significance of the host cellular immune response in patients with EBVaGC have not been thoroughly elucidated. Therefore, further research is necessary to better understand the role of tumor microenvironment in EBVaGC.

No MeSH data available.


Related in: MedlinePlus