Interspatial Distribution of Tumor and Immune Cells in Correlation with PD-L1 in Molecular Subtypes of Gastric Cancers

Dislich, Bastian; Mertz, Kirsten D.; Gloor, Beat; Langer, Rupert

doi:10.3390/cancers14071736

Cited by 7 publications

(3 citation statements)

References 36 publications

(57 reference statements)

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“…The expression of these anti-tumor immunity molecules is also characteristic of a T cell-inflamed phenotype [ 65 ]. Our bioinformatic observations are supported by many other reports that EBVaGCs express higher levels of PDL1 protein [ 66 , 67 , 68 , 69 , 70 , 71 ]. In vitro work has also definitively shown that many EBVaGC cell lines expressed high levels of PDL1, which functionally contributed to the suppression of T cell proliferation [ 71 ].…”

Section: Discussionsupporting

confidence: 89%

Tumor-Infiltrating T Cells in EBV-Associated Gastric Carcinomas Exhibit High Levels of Multiple Markers of Activation, Effector Gene Expression, and Exhaustion

Salnikov

Prusinkiewicz

Lin

et al. 2023

Viruses

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Epstein–Barr virus (EBV) is a gamma-herpesvirus associated with 10% of all gastric cancers (GCs) and 1.5% of all human cancers. EBV-associated GCs (EBVaGCs) are pathologically and clinically distinct entities from EBV-negative GCs (EBVnGCs), with EBVaGCs exhibiting differential molecular pathology, treatment response, and patient prognosis. However, the tumor immune landscape of EBVaGC has not been well explored. In this study, a systemic and comprehensive analysis of gene expression and immune landscape features was performed for both EBVaGC and EBVnGC. EBVaGCs exhibited many aspects of a T cell-inflamed phenotype, with greater T and NK cell infiltration, increased expression of immune checkpoint markers (BTLA, CD96, CTLA4, LAG3, PD1, TIGIT, and TIM3), and multiple T cell effector molecules in comparison with EBVnGCs. EBVaGCs also displayed a higher expression of anti-tumor immunity factors (PDL1, CD155, CEACAM1, galectin-9, and IDO1). Six EBV-encoded miRNAs (miR-BARTs 8-3p, 9-5p, 10-3p, 22, 5-5p, and 14-3p) were strongly negatively correlated with the expression of immune checkpoint receptors and multiple markers of anti-tumor immunity. These profound differences in the tumor immune landscape between EBVaGCs and EBVnGCs may help explain some of the observed differences in pathological and clinical outcomes, with an EBV-positive status possibly being a potential biomarker for the application of immunotherapy in GC.

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Section: Discussionsupporting

confidence: 89%

Tumor-Infiltrating T Cells in EBV-Associated Gastric Carcinomas Exhibit High Levels of Multiple Markers of Activation, Effector Gene Expression, and Exhaustion

Salnikov

Prusinkiewicz

Lin

et al. 2023

Viruses

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“…In nearly all cases, CD8+ TILs were present both in the tumor and the stromal compartment and correlated with PD-L1 positivity, which is in agreement with many previous studies. In contrast with previous studies on MSI-positive tumors, we found MSI positivity to be mutually exclusive with CD8+ TILs and nearly also with PD-L1 expression [ 38 , 39 , 40 ]. This may be due to the fact that we only applied PMS2, MLH1, MSH2, and MSH6 immunohistochemistry without the possibility to confirm our results by multiplex PCR.…”

Section: Discussioncontrasting

confidence: 99%

Biomarkers for Immunotherapy in Poorly Differentiated Sinonasal Tumors

et al. 2022

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The sinonasal cavities harbor a wide variety of rare cancer types. Histopathological classification can be challenging, especially for poorly differentiated tumors. Despite advances in surgery and radio-chemotherapy, the 5-year survival rate is still very low. Thus, there is an unmet clinical need for new therapeutic options. We retrospectively evaluated poorly differentiated tumors of 9 different histological subtypes from 69 patients who had received conventional treatments for the presence of CD8+ tumor-infiltrating lymphocytes (TILs), as well as the expression of PD-L1 and microsatellite instability (MSI) markers MLH1, MSH2, MSH6 and PMS2, as biomarkers for immunotherapy. CD8+ TILs were present in 23/69 (33%) cases, PD-L1 expression was observed in 23/69 (33%), and markers for MSI positivity in 5/69 (7%) cases. CD8+ TILs correlated with PD-L1 positivity, while both were mutually exclusive with MSI markers. None of the biomarkers were associated with clinical features as age, gender or tumor stage. Cases with CD8+ TILs and PD-L1 positivity showed a tendency toward worse disease-specific survival. Immune checkpoint inhibitors are emerging as new options for treatment of many tumor types. Our results indicate that also a substantial subset of patients with poorly differentiated sinonasal tumors may be a candidate to be treated with this promising new therapy.

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“…Some existing studies propose using EBV as an adjuvant predictor of immune response in GC patients [84]. For example, combining PD-L1 and CD8 could identify EBVaGCs with high immunoreactivity in patients with pMMR [85]. A real-world study by Yu et al found that better ORR and PFS were observed only in EBVaGC patients when they were combined with CPS ≥ 1 [86].…”

Section: Epstein-barr Virus Status As the Biomarker For Gc Immunotherapymentioning

confidence: 99%

Predictive Biomarkers for Immunotherapy in Gastric Cancer: Current Status and Emerging Prospects

Hou,

Zhao,

Zhu

2023

IJMS

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Gastric cancer presents substantial management challenges, and the advent of immunotherapy has ignited renewed hope among patients. Nevertheless, a significant proportion of patients do not respond to immunotherapy, and adverse events associated with immunotherapy also occur on occasion, underscoring the imperative to identify suitable candidates for treatment. Several biomarkers, including programmed death ligand-1 expression, tumor mutation burden, mismatch repair status, Epstein–Barr Virus infection, circulating tumor DNA, and tumor-infiltrating lymphocytes, have demonstrated potential in predicting the effectiveness of immunotherapy in gastric cancer. However, the quest for the optimal predictive biomarker for gastric cancer immunotherapy remains challenging, as each biomarker carries its own limitations. Recently, multi-omics technologies have emerged as promising platforms for discovering novel biomarkers that may help in selecting gastric cancer patients likely to respond to immunotherapy. The identification of reliable predictive biomarkers for immunotherapy in gastric cancer holds the promise of enhancing patient selection and improving treatment outcomes. In this review, we aim to provide an overview of clinically established biomarkers of immunotherapy in gastric cancer. Additionally, we introduce newly reported biomarkers based on multi-omics studies in the context of gastric cancer immunotherapy, thereby contributing to the ongoing efforts to refine patient stratification and treatment strategies.

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Interspatial Distribution of Tumor and Immune Cells in Correlation with PD-L1 in Molecular Subtypes of Gastric Cancers

Cited by 7 publications

References 36 publications

Tumor-Infiltrating T Cells in EBV-Associated Gastric Carcinomas Exhibit High Levels of Multiple Markers of Activation, Effector Gene Expression, and Exhaustion

Tumor-Infiltrating T Cells in EBV-Associated Gastric Carcinomas Exhibit High Levels of Multiple Markers of Activation, Effector Gene Expression, and Exhaustion

Biomarkers for Immunotherapy in Poorly Differentiated Sinonasal Tumors

Predictive Biomarkers for Immunotherapy in Gastric Cancer: Current Status and Emerging Prospects

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