Prognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC

Abstract Background: Hepatocellular carcinoma (HCC) is the second most common cancer-associated cause of death globally. It is thus vital that novel diagnostic and prognostic biomarkers associated with early-stage HCC be identified. While keratin 17 (KRT17) has previously been reported to be associated with certain cancer types, its relationship with HCC remains to be defined. Methods：The expression of KRT17 in the TCGA LIHC database and in 44 pairs of HCC patient samples was assessed via qRT-PCR, western blotting, and immunohistochemical staining. The prognostic relevance of KRT17 was assessed using Kaplan-Meir curves, while important cancer- and KRT17-related biological processes were defined through gene set enrichment analysis (GSEA). The functional link between KRT17 expression and tumor cell proliferation/survival was assessed through flow cytometry, colony formation assay, CCK-8 assay, and subcutaneous tumor model approaches. Protein-protein interaction (PPI) networks and analyses of immune cell infiltration were also employed to define key signaling pathways associated with KRT17 expression in HCC. Results：HCC tissue samples exhibited increased KRT17 mRNA and protein expression that was predictive of poorer patient survival (P<0.001). GSEA and functional experiments revealed that KRT17 functioned as a regulator of HCC tumor cell survival, proliferation, and cell cycle progression in vitro and in vivo. PPI network analyses also revealed that KRT17 expression was linked to immune cell infiltration and activation in patients with HCC. Conclusion: We found that increased KRT17 levels were associated with poorer survival, more aggressive disease, and altered immune cell infiltration in patients suffering from HCC. As such, KRT17 may function as an oncogene and a prognostic biomarker in this cancer type.

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Abstract A054: Tumor cell intrinsic factors dictate immune cell infiltration and response to immunotherapy

10.1158/2326-6074.cricimteatiaacr18-a054 ◽

2019 ◽

Author(s):

Katelyn T. Byrne ◽

Jinyang Li ◽

Robert H. Vonderheide ◽

Ben Stanger

Keyword(s):

Tumor Cell ◽

Immune Cell ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Intrinsic Factors

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Opposite Roles of Tumor Cell Proliferation and Immune Cell Infiltration in Postoperative Liver Metastasis of PDAC

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.714718 ◽

2021 ◽

Vol 9 ◽

Author(s):

Guangfu Wang ◽

Shangnan Dai ◽

Hao Gao ◽

Yong Gao ◽

Lingdi Yin ◽

...

Keyword(s):

Pancreatic Cancer ◽

Immune Response ◽

Cell Proliferation ◽

T Cells ◽

Liver Metastasis ◽

Tumor Cell ◽

Immune Cell ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Tumor Cell Proliferation

BackgroundRecurrence of liver metastasis after pancreatectomy is often a predictor of poor prognosis. Comprehensive genomic analysis may contribute to a better understanding of the molecular mechanisms of postoperative liver metastasis and provide new therapeutic targets.MethodsA total of 67 patients from The Cancer Genome Atlas (TCGA) were included in this study. We analyzed differentially expressed genes (DEGs) by R package “DESeq2.” Weighted gene co-expression network analysis (WGCNA) was applied to investigate the key modules and hub genes. Immunohistochemistry was used to analyze tumor cell proliferation index and CD4+ T cells infiltration.ResultsFunctional analysis of DEGs between the liver metastatic and recurrence-free groups was mainly concentrated in the immune response. The liver metastasis group had lower immune and stroma scores and a higher TP53 mutation rate. WGCNA showed that the genes in key modules related to disease-free survival (DFS) and overall survival (OS) were mainly enriched in the cell proliferation process and tumor immune response. Immunohistochemical analysis showed that the pancreatic cancer cells of patients with early postoperative liver metastasis had higher proliferative activity, while the infiltration of CD4+ T cells in tumor specimens was less.ConclusionOur study suggested that increased immune cell infiltration (especially CD4+ T cells) and tumor cell proliferation may play an opposite role in liver metastasis recurrence after pancreatic cancer.

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Optimal Evaluation of Programmed Death Ligand-1 on Tumor Cells Versus Immune Cells Requires Different Detection Methods

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2017-0159-oa ◽

2018 ◽

Vol 142 (8) ◽

pp. 982-991 ◽

Cited By ~ 16

Author(s):

Kelly A. Schats ◽

Emily A. Van Vré ◽

Carolien Boeckx ◽

Martine De Bie ◽

Dorien M. Schrijvers ◽

...

Keyword(s):

Tumor Cell ◽

Tumor Cells ◽

Immune Cells ◽

Immune Cell ◽

Detection Method ◽

Death Receptor ◽

Detection Methods ◽

Programmed Death Ligand 1 ◽

Cell Staining ◽

Programmed Death

Context.— The benefit of programmed death ligand-1 (PD-L1) immunohistochemistry (IHC) as a method to select patients who may benefit from programmed death receptor-1 (PD-1)/PD-L1 immunotherapies remains uncertain in many tumor indications. Objectives.— To compare the commercially available, approved PD-L1 IHC assays (22C3, 28-8, SP142, SP263), specifically identifying the changes in staining output created by altering the detection method. Design.— This pilot study investigates the respective PD-L1 kit assay staining patterns and related scoring of tumor cells and immune cells on lung carcinoma and melanoma. Furthermore, the influence of the detection method (platform and related reagents) on PD-L1 antibody performance is studied. Results.— The SP142 kit reveals more immune cell staining but less tumor cell staining than the other PD-L1 kits. Alternatively, the 22C3 and 28-8 kits show good tumor cell sensitivity, but less pronounced immune cell staining, even in tonsil. Tumor cell staining by the SP263 kit is comparable to that of 22C3 and 28-8 kits, while immune cell staining is better. Strikingly, the selection of the detection method has a major impact on the sensitivity of the assay for PD-L1 detection per cell type. Switching the detection method of the kits could largely circumvent the observed staining differences. Conclusions.— The diverse sensitivities caused by the choice of the detection method should be taken into consideration when selecting PD-L1 kits or developing PD-L1 IHC laboratory-developed tests. When using alternative kits or laboratory-developed tests, it is strongly recommended to reestablish their clinical utility per therapeutic agent or compare them with the original kit.

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Combined PD-1/PD-L1 and tumor-infiltrating immune cells redefined a unique molecular subtype of high-grade serous ovarian carcinoma

BMC Genomics ◽

10.1186/s12864-021-08265-y ◽

2022 ◽

Vol 23 (1) ◽

Author(s):

Ping Liu ◽

Ruoxu Chen ◽

Xudong Zhang ◽

Ruiting Fu ◽

Lin Tao ◽

...

Keyword(s):

Ovarian Carcinoma ◽

Immune Cell ◽

Molecular Subtype ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

High Grade ◽

Serous Ovarian Carcinoma ◽

Programmed Death ◽

Programmed Death 1 ◽

Antigen Presenting

Abstract Background High-grade serous ovarian carcinoma is highly heterogeneous, and although many studies have been conducted to identify high-grade serous ovarian carcinoma molecular subtypes that are sensitive to immunotherapy, no precise molecular subtype has been proposed to date. Immune cell infiltration and immune checkpoints are highly correlated with immunotherapy. Here, we investigated immune cell infiltration and immune checkpoint values for prognosis and precise immunotherapy for high-grade serous ovarian carcinoma based on molecular subtype classification. Results “High antigen-presenting cells infiltration molecular subtype of high-grade serous ovarian carcinoma” was identified in immune cell infiltration profiles. Each of the three immune cell infiltration clusters (A, B, and C) demonstrated distinct immune cell characterization, with immune cell infiltration cluster C exhibiting high antigen-presenting cell infiltration, improved prognosis, and higher sensitivity to immunotherapy. Programmed death-1/programmed death ligand 1 has a prognostic and predictive role that can help classify molecular subtypes. Conclusions Our findings redefined a unique molecular subtype of high-grade serous ovarian carcinoma, suggesting that high-grade serous ovarian carcinoma patients with higher antigen-presenting cell infiltration and programmed death-1/programmed death ligand 1 expression can benefit from precise immunotherapy.

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Tumor Cell-Intrinsic Factors Underlie Heterogeneity of Immune Cell Infiltration and Response to Immunotherapy

Immunity ◽

10.1016/j.immuni.2018.06.006 ◽

2018 ◽

Vol 49 (1) ◽

pp. 178-193.e7 ◽

Cited By ~ 149

Author(s):

Jinyang Li ◽

Katelyn T. Byrne ◽

Fangxue Yan ◽

Taiji Yamazoe ◽

Zeyu Chen ◽

...

Keyword(s):

Tumor Cell ◽

Immune Cell ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Intrinsic Factors

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Tissue remodeling and cell signaling underpin changes in tumor microenvironment heterogeneity in glioma oncogenesis

10.1101/2021.12.05.471299 ◽

2021 ◽

Author(s):

Marija Dinevska ◽

Samuel S. Widodo ◽

Liam Furst ◽

Lucero Cuzcano ◽

Yitong Fang ◽

...

Keyword(s):

Extracellular Matrix ◽

Tumor Microenvironment ◽

Tumor Cell ◽

Cancer Cells ◽

Immune Cell ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

High Grade ◽

Matrix Deposition ◽

Extracellular Matrix Deposition

ABSTRACTBrain tumor cells thrive by adapting to the signals in their microenvironment. Understanding how the tumor microenvironment evolves during disease progression is crucial to deciphering the mechanisms underlying the functional behavior of cancer cells. To adapt, cancer cells activate signaling and transcriptional programs and migrate to establish micro-niches, in response to signals from neighboring cells and non-cellular stromal factors. Using multiple tissue analysis approaches to identify and measure immune cell infiltration and extracellular matrix deposition in brain tumors, we show that low-grade glioma is largely devoid of infiltrating immune cells and extracellular matrix proteins, while high-grade glioma exhibits abundant immune cell infiltration and activation, as well as extensive collagen deposition. Spatial analysis shows that most T-cells are sequestered in perivascular nests, but macrophages penetrate deep into tumor cell rich regions. High-grade gliomas exhibit heterogeneous PI3K and MAPK signaling, which correlates with distinct pathological hallmarks, including tumor angiogenesis, tumor cell density and extracellular matrix deposition. Our results also provide compelling evidence that tissue remodeling is an important element in glioma progression, and that targeting the extracellular matrix will be critical to improving GBM therapy.

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PD-L1 (SP142) testing is concordant between Benchmark Ultra and Bond-III stainers

World Journal of Urology ◽

10.1007/s00345-021-03828-w ◽

2021 ◽

Author(s):

Eva Compérat ◽

André Oszwald ◽

Gabriel Wasinger ◽

Justine Wacquet ◽

Morgan Rouprêt ◽

...

Keyword(s):

Bladder Cancer ◽

Tumor Cell ◽

Immune Cell ◽

Invasive Disease ◽

Serial Sections ◽

Programmed Death Ligand 1 ◽

Non Invasive ◽

Metastatic Bladder Cancer ◽

Programmed Death ◽

Immune Cell Score

Abstract Background Atezolizumab is an inhibitor of programmed death-ligand 1 (PD-L1), used to treat advanced or metastatic bladder cancer, and in trials for non-invasive disease. In order to be eligible for treatment, patients require a PD-L1 immune cell score ≥ 5%, using the Ventana SP142 PD-L1 assay. Many laboratories do not have access to the required Ventana Benchmark Ultra stainer, and it is unclear if the assay performs similarly on other stainers. In this study, we compare SP142 assay results between Ventana Benchmark Ultra and Leica Bond-III stainers. Methods Serial sections of 90 samples of transurethral bladder resections (comprising 51 pTaHG, 8 pTis, 18 pT1, 10 pT2 tumors) were stained using the SP142 PD-L1 antibody on Ventana Benchmark Ultra and Leica Bond-III stainers, manually scored, and compared using accuracy and Cohen’s kappa measures. Results Both devices yielded highly concordant PD-L1 immune cell scores (accuracy 0.84, Cohen’s κ 0.732). Moreover, we found similar tumor cell (TC) PD-L1 scores using both stainers, and a trend towards greater TC scores in pT2 stage samples (p = 0.05). Conclusion This study is the first to compare the SP142 antibody in bladder cancer on two different stainers. Our results indicate that both Benchmark Ultra and Bond-III stainers yield highly concordant results using the SP142 PD-L1 antibody.

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