Incorporating Immunotherapy in the Management of Gastric Cancer: Molecular and Clinical Implications

Agnarelli, Alessandro; Vella, Viviana; Samuels, Mark E.; Papanastasopoulos, Panagiotis; Giamas, Georgios

doi:10.3390/cancers14184378

Cited by 8 publications

(4 citation statements)

References 167 publications

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“…Finally, as previously mentioned, the expression of PD‐L1 in GC is only a surrogate indicator of patient response to immunotherapy. Indeed, some other factors besides tumour expression of PD‐L1 has also been associated with the response to immunotherapy in patients with various cancers, such as MIS of the cancer, and the status of the Epstein–Barr virus infection 50 . Large‐scale clinical studies evaluating the effect of PD‐1/PD‐L1 blockade therapy on the survival of patients with GC should be evaluated according to the HP infective status in the future.…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori infection and PD‐L1 expression in gastric cancer: A meta‐analysis

Zhu

et al. 2022

Eur J Clin Investigation

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Background High expression of programmed death ligand‐1 (PD‐L1) has been related to good response to immunotherapy patients with gastric cancer (GC). However, the influence of Helicobacter pylori (HP) infection on PD‐L1 expression in GC remains unknown. A meta‐analysis was performed to evaluate the association between HP infection and PD‐L1 expression in GC. Methods Observational studies that investigated the relationship between HP infection and PD‐L1 expression in patients with GC were obtained by search electronic databases, including PubMed, Embase, Cochrane's Library and Web of Science. A random‐effect model incorporating the possible influence of between‐study heterogeneity was used to pool the results. Results Ten studies with 1870 patients with GC contributed to the meta‐analysis. Pooled results showed that HP infection was significantly associated with the tumour expression of PD‐L1 (odds ratio [OR]: 1.90, 95% confidence interval: 1.33–2.72, p < .001; I2 = 53%). Subgroup analyses showed that the association between HP infection and PD‐L1 expression in GC was not significantly affected by sample size, methods for PD‐L1 evaluation and quality score (p for subgroup analyses all >.05). However, a stronger association was observed in studies with higher prevalence of HP infection (≥35%, OR: 2.58) as compared with those with lower prevalence (<35%, OR: 1.45, p for subgroup difference = .04). Conclusion Helicobacter pylori infection in GC patients is associated with tumour expression of PD‐L1, suggesting HP infection may be a predictor of good response to immunotherapy in GC.

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Section: Discussionmentioning

confidence: 99%

Helicobacter pylori infection and PD‐L1 expression in gastric cancer: A meta‐analysis

Zhu

et al. 2022

Eur J Clin Investigation

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“…Apart from antibodies, a number of other immunotherapeutic treatment options are being considered for treatment of EBVaGCs ( 239 – 241 ). One such option is chimeric antigen receptor (CAR) T cell therapy, with multiple clinical trials recruiting GC patients for these studies (NCT05583201, NCT05393986, NCT05396300, NCT04650451).…”

Section: Immunotherapy and Other Treatmentsmentioning

confidence: 99%

The viral etiology of EBV-associated gastric cancers contributes to their unique pathology, clinical outcomes, treatment responses and immune landscape

Salnikov,

MacNeil,

Mymryk

2024

Front. Immunol.

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Epstein-Barr virus (EBV) is a pathogen known to cause a number of malignancies, often taking years for them to develop after primary infection. EBV-associated gastric cancer (EBVaGC) is one such malignancy, and is an immunologically, molecularly and pathologically distinct entity from EBV-negative gastric cancer (EBVnGC). In comparison with EBVnGCs, EBVaGCs overexpress a number of immune regulatory genes to help form an immunosuppressive tumor microenvironment (TME), have improved prognosis, and overall have an “immune-hot” phenotype. This review provides an overview of the histopathology, clinical features and clinical outcomes of EBVaGCs. We also summarize the differences between the TMEs of EBVaGCs and EBVnGCs, which includes significant differences in cell composition and immune infiltration. A list of available EBVaGC and EBVnGC gene expression datasets and computational tools are also provided within this review. Finally, an overview is provided of the various chemo- and immuno-therapeutics available in treating gastric cancers (GCs), with a focus on EBVaGCs.

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“…Therefore, the only established and broadly available biomarkers for GC treatment are HER2 amplification, MSI-H, and PD-L1 expression [ 29 ]. The therapeutic arsenal for GC is limited when compared to other tumor types, and current therapies have not significantly improved patient prognosis [ 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Classifications in Gastric Cancer: A Call for Interdisciplinary Collaboration

Díaz del Arco,

Fernández Aceñero,

Ortega Medina

2024

IJMS

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Gastric cancer (GC) is a heterogeneous disease, often diagnosed at advanced stages, with a 5-year survival rate of approximately 20%. Despite notable technological advancements in cancer research over the past decades, their impact on GC management and outcomes has been limited. Numerous molecular alterations have been identified in GC, leading to various molecular classifications, such as those developed by The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG). Other authors have proposed alternative perspectives, including immune, proteomic, or epigenetic-based classifications. However, molecular stratification has not yet transitioned into clinical practice for GC, and little attention has been paid to alternative molecular classifications. In this review, we explore diverse molecular classifications in GC from a practical point of view, emphasizing their relationships with clinicopathological factors, prognosis, and therapeutic approaches. We have focused on classifications beyond those of TCGA and the ACRG, which have been less extensively reviewed previously. Additionally, we discuss the challenges that must be overcome to ensure their impact on patient treatment and prognosis. This review aims to serve as a practical framework to understand the molecular landscape of GC, facilitate the development of consensus molecular categories, and guide the design of innovative molecular studies in the field.

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Incorporating Immunotherapy in the Management of Gastric Cancer: Molecular and Clinical Implications

Cited by 8 publications

References 167 publications

Helicobacter pylori infection and PD‐L1 expression in gastric cancer: A meta‐analysis

Helicobacter pylori infection and PD‐L1 expression in gastric cancer: A meta‐analysis

The viral etiology of EBV-associated gastric cancers contributes to their unique pathology, clinical outcomes, treatment responses and immune landscape

Molecular Classifications in Gastric Cancer: A Call for Interdisciplinary Collaboration

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