PD-L1 Expression Level Displays a Positive Correlation with Immune Response in Pancreatic Cancer

Zhao, Lei; Cao, Yaming

doi:10.1155/2020/8843146

Cited by 7 publications

(5 citation statements)

References 44 publications

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“…The importance of ‘PDL-1 combined score’ for gastrointestinal tumors has been emphasized in the updated College of American Pathologists (CAP) Protocols in June 2021, but it was also controversial for gastrointestinal tumors in the literature. 32 , 33 , 34 , 35 Twenty-nine patients for whom we detected a positive combine score for PDL-1 had higher survival numerically (30.6 months vs. 17 months, P = .57). Our statistically insignificant results might also be related to small sample.…”

Section: Discussionmentioning

confidence: 75%

Prognostic Value of Tissue-Resident Memory T Cells and Tumor Microenvironmental Features in Resected Pancreatic Adenocarcinoma

Başoğlu¹,

Akar²,

Bağcı³

et al. 2021

Balkan Med J

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Background: Pancreatic ductal adenocarcinoma differs from other solid tumors with its unique immunosuppressive microenvironment and non-immunogenic feature. There are not many studies in the literature investigating the effect of these features on prognosis. Aims: To investigate the prognostic value of tissue-resident memory T cells, tumor microenvironment features, and tumor-associated immune cells in resected pancreatic ductal adenocarcinomas. Study Design: Retrospective cross-sectional study. Methods: Of 138 patients diagnosed with pancreatic ductal adenocarcinoma between 2011 and 2018, 81 were included in the study. Specimens from operated patients were reassessed separately as peritumoral and intratumoral areas for tissue resident memory cells and tumor microenvironmental elements (tumor infiltrating lymphocytes, tumor stroma, CD204+ macrophages, PDL1+ immune cells). Disease-free survival and overall survival were defined from the date of operation to the date of recurrence and the date of first diagnosis to the date of death, respectively. If the patient was alive, the last visit date was taken into account. Results: The median age at diagnosis was 63 (range: 40-78). The median follow-up period was 18.9 months (range: 1.4-80.4 months). Median overall survival was 23.7 months (1.4-80.4 months) and median disease-free survival was 10.8 months (1.4-74.4 months). Patients with higher intra-tumoral tissue-resident memory cell counts had a longer survival trend than those having lower values (25.6 months vs. 18 months, respectively, P = .84). According to microenvironmental evaluations, lower stromal score (defined as stroma having less desmoplasia and rich in cells) and presence of peritumoral Crohn’s-like inflammatory response were associated with higher survival (29.2 months vs. 19.7 months for low vs. high stromal scores, respectively, P = .16 and 30.2 months vs. 18.1 months for the presence of Crohn’s-like inflammatory response P = .13). Decreased survival was observed in tumors with increased CD204+ tumor-associated macrophages which were immunosuppressive elements of the microenvironment (12 months vs. 26.3 months for intra-tumoral assessment, P = .29). Conclusion: Tissue-resident memory T cells and other microenvironmental features may be prognostic in resectable pancreatic ductal adenocarcinomas. Further studies with larger cohorts are needed for validation.

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Section: Discussionmentioning

confidence: 75%

Prognostic Value of Tissue-Resident Memory T Cells and Tumor Microenvironmental Features in Resected Pancreatic Adenocarcinoma

Başoğlu¹,

Akar²,

Bağcı³

et al. 2021

Balkan Med J

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“…Immunotherapy is a promising treatment that has revealed considerable efficacy in numerous tumors, including melanoma, non-small cell lung cancer, renal cell carcinoma, hepatocellular carcinoma, and Hodgkin's lymphoma (83)(84)(85). However, pancreatic cancer does not appear to be sensitive to immunotherapy, with a low overall response rate.…”

Section: Discussionmentioning

confidence: 99%

Characterization of neuroendocrine regulation- and metabolism-associated molecular features and prognostic indicators with aid to clinical chemotherapy and immunotherapy of patients with pancreatic cancer

et al. 2023

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The worldwide prevalence of pancreatic cancer has been rising in recent decades, and its prognosis has not improved much. The imbalance of substance and energy metabolism in tumour cells is among the primary causes of tumour formation and occurrence, which is often controlled by the neuroendocrine system. We applied Cox and LASSO regression analysis to develop a neuroendocrine regulation- and metabolism-related prognostic risk score model with three genes (GSK3B, IL18 and VEGFA) for pancreatic cancer. TCGA dataset served as the training and internal validation sets, and GSE28735, GSE62452 and GSE57495 were designated as external validation sets. Patients classified as the low-risk population (category, group) exhibited considerably improved survival duration in contrast with those classified as the high-risk population, as determined by the Kaplan-Meier curve. Then, we combined all the samples, and divided them into three clusters using unsupervised clustering analysis. Unsupervised clustering, t-distributed stochastic neighbor embedding (t-SNE), and principal component analysis (PCA) were further utilized to demonstrate the reliability of the prognostic model. Moreover, the risk score was shown to independently function as a predictor of pancreatic cancer in both univariate and multivariate Cox regression analyses. The results of gene set enrichment analysis (GSEA) illustrated that the low-risk population was predominantly enriched in immune-associated pathways. “ESTIMATE” algorithm, single-sample GSEA (ssGSEA) and the Tumor Immune Estimation Resource (TIMER) database showed immune infiltration ratings were enhanced in the low-risk category in contrast with the high-risk group. Tumour immune dysfunction and exclusion (TIDE) database predicted that immunotherapy for pancreatic cancer may be more successful in the high-risk than in the low-risk population. Mutation analysis illustrated a positive link between the tumour mutation burden and risk score. Drug sensitivity analysis identified 44 sensitive drugs in the high- and low-risk population. GSK3B expression was negatively correlated with Oxaliplatin, and IL18 expression was negatively correlated with Paclitaxel. Lastly, we analyzed and verified gene expression at RNA and protein levels based on GENPIA platform, HPA database and quantitative real-time PCR. In short, we developed a neuroendocrine regulation- and metabolism-associated prognostic model for pancreatic cancer that takes into account the immunological microenvironment and drug sensitivity.

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“…However, for IFN-γ and PD-L1 in the metastatic setting, the group with a better prognosis had serum levels above the cut-off value. IFN-γ has been described to inhibit the proliferation and migration of PDAC (Lange et al 2011 ; Zhang et al 2018 ), however, high PD-L1 expression on pancreatic cancer cells has been associated with a poor prognosis in multiple previous studies (Nomi et al 2007 ; Gao et al 2018 ; Hu et al 2019 ; Zhao and Cao 2020 ). But the same might not hold true for serum levels of PD-L1.…”

Section: Discussionmentioning

confidence: 99%

Serum biomarker panel diagnostics in pancreatic ductal adenocarcinoma: the clinical utility of soluble interleukins, IFN-γ, TNF-α and PD-1/PD-L1 in comparison to established serum tumor markers

Dorman

Gerckens

Krüger

et al. 2022

J Cancer Res Clin Oncol

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Purpose Novel biomarkers to better predict outcome and select the best therapeutic strategy for the individual patient are necessary for pancreatic ductal adenocarcinoma (PDAC). Methods Using a panel assay, multiple biomarkers (IFN-γ, IL-10, IL-6, IL-8, TNF-α, CEA, CA 19–9, CYFRA 21–1, HE4, PD-1 and PD-L1 levels) were measured in serum samples of 162 patients with resected, locally advanced and metastatic PDAC in this retrospective single-center study. Optimal cut-off values to differentiate prognostic subgroups with significantly different overall survival (OS) were determined by receiver operator characteristics and Youden Index analysis. Marker levels were assessed before the start of chemotherapy and correlated with OS by univariate and multivariate Cox analysis. Results Median OS for resected patients was 28.2 months, for locally advanced patients 17.9 months and for patients with metastatic disease 8.6 months. CYFRA 21–1 and IL-8 discriminated metastatic from locally advanced patients best (AUC 0.85 and AUC 0.81, respectively). In univariate analyses, multiple markers showed prognostic relevance in the various subgroups. However, multivariate Cox models comprised only CYFRA 21–1 in the resected group (HR 1.37, p = 0.015), IL-10 in locally advanced PDAC (HR 10.01, p = 0.014), as well as CYFRA 21–1 and CA 19–9 in metastatic PDAC (p = 0.008 and p = 0.010) as an independent prognostic marker for overall survival. Conclusion IL-10 levels may have independent prognostic value in locally advanced PDAC, whereas CYFRA 21–1 levels are prognostic after PDAC surgery. CYFRA 21–1 and IL-8 have been identified to best discriminate metastatic from locally advanced patients.

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PD-L1 Expression Level Displays a Positive Correlation with Immune Response in Pancreatic Cancer

Cited by 7 publications

References 44 publications

Prognostic Value of Tissue-Resident Memory T Cells and Tumor Microenvironmental Features in Resected Pancreatic Adenocarcinoma

Prognostic Value of Tissue-Resident Memory T Cells and Tumor Microenvironmental Features in Resected Pancreatic Adenocarcinoma

Characterization of neuroendocrine regulation- and metabolism-associated molecular features and prognostic indicators with aid to clinical chemotherapy and immunotherapy of patients with pancreatic cancer

Serum biomarker panel diagnostics in pancreatic ductal adenocarcinoma: the clinical utility of soluble interleukins, IFN-γ, TNF-α and PD-1/PD-L1 in comparison to established serum tumor markers

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