PD-L1 expression in carcinoma of the esophagogastric junction is positively correlated with T-cell infiltration and overall survival

Knief, Juliana; Lazar-Karsten, Pamela; Hummel, Richard; Wellner, Ulrich F.; Thorns, Christoph

doi:10.1016/j.prp.2019.03.030

Cited by 15 publications

(18 citation statements)

References 43 publications

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“…Similarly, there are many factors related to the immune microenvironment that also predict whether a patient will respond to single-agent PD-1 inhibition. Such factors include high tumor antigen load, dendritic cells, CD4+T cell infiltration, CD8+T cell infiltration, and pro-inflammatory cytokines, among others [32][33][34][35]. The most well-known cytokine responsible for PD-L1 upregulation in the gastrointestinal tract is the regulatory cytokine interleukin 10 (IL10) [36].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis identifies COL1A1, THBS2 and SPP1 as potential predictors of patient prognosis and immunotherapy response in gastric cancer

et al. 2021

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Background: The present study aimed to use bioinformatics tools to explore pivotal genes associated with the occurrence of gastric cancer (GC) and assess their prognostic significance, and link with clinicopathological parameters. We also investigated the predictive role of COL1A1, THBS2, and SPP1 in immunotherapy. Materials and methods: We identified differential genes (DEGs) that were up- and down-regulated in the three datasets (GSE26942, GSE13911, and GSE118916) and created protein–protein interaction (PPI) networks from the overlapping DEGs. We then investigated the potential functions of the hub genes in cancer prognosis using PPI networks, and explored the influence of such genes in the immune environment. Results: Overall, 268 overlapping DEGs were identified, of which 230 were up-regulated and 38 were down-regulated. CytoHubba selected the top ten hub genes, which included SPP1, TIMP1, SERPINE1, MMP3, COL1A1, BGN, THBS2, CDH2, CXCL8, and THY1. With the exception of SPP1, survival analysis using the Kaplan–Meier database showed that the levels of expression of these genes were associated with overall survival. Genes in the most dominant module explored by MCODE, COL1A1, THBS2, and SPP1, were primarily enriched for two KEGG pathways. Further analysis showed that all three genes could influence clinicopathological parameters and immune microenvironment, and there was a significant correlation between COL1A1, THBS2, SPP1, and PD-L1 expression, thus indicating a potential predictive role for GC response to immunotherapy. Conclusion: ECM–receptor interactions and focal adhesion pathways are of great significance in the progression of GC. COL1A1, THBS2, and SPP1 may help predict immunotherapy response in GC patients.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis identifies COL1A1, THBS2 and SPP1 as potential predictors of patient prognosis and immunotherapy response in gastric cancer

et al. 2021

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“…45,46,48 Further study is needed to address whether PD-L1 status differs according to tumor location in EGJ adenocarcinoma. [45][46][47][48] Beyond TCGA molecular subtypes, the Asian Cancer Research…”

Section: Epstein-barr Virus-associated Tumors Show Hypermethylationmentioning

confidence: 99%

Esophagogastric junction adenocarcinoma shares characteristics with gastric adenocarcinoma: Literature review and retrospective multicenter cohort study

Imamura

Watanabe

Oki

et al. 2020

Annals of Gastroent Surgery

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The incidence of esophagogastric junction (EGJ) adenocarcinoma has been gradually increasing in Asia, just like in Western countries a few decades ago. Despite recent advances in next‐generation sequencing and multimodal treatments, EGJ adenocarcinoma is still an aggressive malignancy with poor outcomes. Clinically, EGJ adenocarcinoma can be separated into Barrett's adenocarcinoma and cardiac adenocarcinoma, with frequent similarities observed. Barrett's adenocarcinoma is likely to be of gastric origin in terms of its premalignant background, risk factors, and stem cell regulators. Recent comprehensive genomic analyses suggest that immunotherapy may be essential for high‐level microsatellite instability (MSI‐H)‐ and Epstein‐Barr virus (EBV)‐associated subtypes, and against the immunosuppressive phenotype in genomically stable (GS) subtypes, in the treatment of EGJ and gastric adenocarcinoma. Although the chromosomal instability (CIN) subtype dominates EGJ adenocarcinoma, there is still a need to investigate the other molecular subtypes and their targets. Because of the distinctive characteristics of tumor location of EGJ adenocarcinoma, we also described the results of a multicenter cohort study of EGJ adenocarcinoma, comparing Siewert type I (distal esophagus), II (cardia of the stomach), and III (subcardia) tumors. We show that type I tumors were frequently accompanied by Barrett's esophagus (78%, P < .0001), with a significantly unfavorable outcome (multivariate EGJ‐cancer‐specific mortality hazard ratio = 1.81, 95% CI, 1.06‐2.97; P = .031). In addition, over half (56%) of these cases experienced disease recurrence in the lymph nodes. Our findings suggest that Barrett's adenocarcinoma may be an aggressive phenotype of EGJ adenocarcinoma due to the potential risk of tumor spread through the complex lympho‐vascular network of the esophagus.

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“…In contrast, others have found high tumour cell expression of PD-L1, but similarly, a high prevalence of PD-L1-positive TILs was also observed [109]. A significant positive correlation between the density of CD8 + T-cells and PD-L1 positivity can be seen in OAC patients, although this was not associated with a survival benefit in some studies [108], and worse survival in others [112]. This may be due in part to the variable pattern of TIL infiltration, with a significantly higher number of PD-L1-positive TILs being seen at the invasive margin [107,108].…”

Section: Immune Checkpoint Moleculesmentioning

confidence: 86%

“…A significant positive correlation between the density of CD8 + T-cells and PD-L1 positivity can be seen in OAC patients, although this was not associated with a survival benefit in some studies [108], and worse survival in others [112]. This may be due in part to the variable pattern of TIL infiltration, with a significantly higher number of PD-L1-positive TILs being seen at the invasive margin [107,108]. For PD-L1-negative cases, mean survival for patients with dense CD8 + T-cell infiltrates is almost four-times longer than for patients without T-cell infiltration [108,110].…”

Section: Immune Checkpoint Moleculesmentioning

confidence: 96%

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Understanding the immuno-biology of oesophageal adenocarcinoma: Towards improved therapeutic approaches

Lonie

Barbour

Dolcetti

2021

Cancer Treatment Reviews

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With an incidence that is constantly rising, oesophageal adenocarcinoma (OAC) is becoming an increasing health burden worldwide. Although significant advances in treatment regimens have improved patient outcomes, survival rates for this deadly cancer remain unsatisfactory. This highlights the need to improve current therapeutic approaches and develop novel therapeutic strategies for treating OAC patients. The advent of immunotherapy has revolutionised treatment across a range of malignancies, however outcomes in OAC show modest results. The inherent resistance of OAC to treatment reflects the complex genomic landscape of this cancer, which displays a lack of ubiquitous driver mutations and large-scale genomic alterations along with high tumour and immune heterogeneity. Research into the immune landscape of OAC is limited, and elucidation of the mechanisms surrounding the immune responses to this complex cancer will result in improved therapeutic approaches. This review explores what is known about the immuno-biology of OAC and explores promising therapeutic avenues that may improve responses to immunotherapeutic regimens.

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PD-L1 expression in carcinoma of the esophagogastric junction is positively correlated with T-cell infiltration and overall survival

Cited by 15 publications

References 43 publications

Bioinformatics analysis identifies COL1A1, THBS2 and SPP1 as potential predictors of patient prognosis and immunotherapy response in gastric cancer

Bioinformatics analysis identifies COL1A1, THBS2 and SPP1 as potential predictors of patient prognosis and immunotherapy response in gastric cancer

Esophagogastric junction adenocarcinoma shares characteristics with gastric adenocarcinoma: Literature review and retrospective multicenter cohort study

Understanding the immuno-biology of oesophageal adenocarcinoma: Towards improved therapeutic approaches

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