scholarly journals Prognostic Value of Immune Environment Analysis in Small Bowel Adenocarcinomas with Verified Mutational Landscape and Predisposing Conditions

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2018
Author(s):  
Erkki-Ville Wirta ◽  
Säde Szeto ◽  
Ulrika Hänninen ◽  
Maarit Ahtiainen ◽  
Jan Böhm ◽  
...  
Keyword(s):  
Small Bowel ◽  
Prognostic Value ◽  
Immune Cell ◽  
Small Bowel Adenocarcinoma ◽  
Prognostic Information ◽  
Environment Analysis ◽  
Characterization Methods ◽  
Programmed Death ◽  
Formalin Fixed Paraffin Embedded ◽  
Predisposing Conditions

Background: Small bowel adenocarcinoma (SBA) is a rare yet insidious cancer with poor survival. The abundance of tumour-infiltrating lymphocytes is associated with improved survival, but the role of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway in tumour escape is controversial. We evaluated immune cell infiltration, PD1/PD-L1 expression and their prognostic value in a series of SBAs with previously verified predisposing conditions and exome-wide somatic mutation characterization. Methods: Formalin-fixed paraffin-embedded tissue sections stained for CD3, CD8, PD-L1 and PD-1 were analysed from 94 SBAs. An immune cell score (ICS) was formed from the amount of the CD3 and CD8 positive lymphocytes from the tumour centre and invasive margin. The PD-L1 and PD-1 positive immune cells (ICs) and ICS were combined into a variable called Immunoprofile. Results: High ICS, PD-L1IC and PD-1, individually and combined as Immunoprofile, were prognostic for better patient outcome. Sixty-five (69%) SBAs expressed ≥1% positive PD-L1IC. A high tumour mutation burden was common (19%) and associated with immune markers. Immunoprofile, adjusted for TNM stage, mismatch repair status, tumour location, sex and age were independent prognostic markers for disease-specific and overall survival. Conclusions: Analysing tumoral immune contexture provides prognostic information in SBA. Combining ICS, PD-1 and PD-L1IC as Immunoprofile enhanced the prognostic performance.

Prognostic relevance of programmed death-ligand 1 expression and microsatellite status in small bowel adenocarcinoma

2020 ◽  
Vol 55 (3) ◽  
pp. 321-329
Author(s):  
Johannes Klose ◽  
Felix Lasitschka ◽  
Cornelia Horsch ◽  
Moritz J. Strowitzki ◽  
Thomas Bruckner ◽  
...  
Keyword(s):  
Small Bowel ◽  
Small Bowel Adenocarcinoma ◽  
Programmed Death Ligand 1 ◽  
Prognostic Relevance ◽  
Programmed Death

Programmed death-ligand 1 (PD-L1) expression in cured and not cured testicular and other germ cell tumors (GCT).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 485-485 ◽  
Author(s):  
Brandon David Bernard ◽  
Laurence Albiges ◽  
Sabina Signoretti ◽  
Jesse Novak ◽  
Michelle S. Hirsch ◽  
...  
Keyword(s):  
Immune Cell ◽  
Therapeutic Option ◽  
Germ Cell Tumors ◽  
Unknown Origin ◽  
Mediastinal Tumors ◽  
Formalin Fixed Paraffin ◽  
Programmed Death ◽  
Formalin Fixed Paraffin Embedded ◽  
Tumor Types ◽  
Formalin Fixed

485 Background: PD-L1 is involved in immune regulation and is prognostic in many tumor types. The aim of this study was to assess PD-L1 expression in orchiectomy and metastases (mets) from GCT and to assess for an association with outcome. Methods: Immunohistochemistry (IHC) on whole sections from archival formalin-fixed paraffin-embedded tissue from Dana-Farber Cancer Institute (DFCI) and Gustave Roussy (IGR) was performed using anti-PD-L1 antibody E1L3N. Stained slides were scored semi-quantitatively and assessed independently. At DFCI, PD-L1 was scored as percent of positive tumor cells (TC) and extent of positive immune cell (IC) infiltrate; at IGR, a cut-off of 5% defined positive TC and IC. PD-L1 status was assessed by site, histology and chemotherapy (CT) status. PD-L1 status was correlated with clinical outcome. Most samples at DFCI were pre-CT (74.2%) whereas most at IGR were post-CT (85.4%). Results: IHC from 171 patients with GCT (89 DFCI, 82 IGR) from 1987-2014 was reviewed. The DFCI cohort included 69 orchiectomy, 15 mets and 5 unknown origin with 28 total deaths; the IGR cohort included 26 lung mets, 36 mediastinal or retroperitoneal lymph node mets and 20 primary mediastinal tumors. DFCI had 38 seminoma (S), 50 nonseminoma (NS) and 1 unknown; at IGR, 13 S and 69 NS. In both cohorts, PD-L1 staining in IC was higher in S (DFCI 33/38 moderate (mod)-high (86.8%); IGR 12/13 positive (92.3%)) vs. NS (DFCI 26/50 mod-high (52.0%); IGR 35/68 positive (51.5%)) (DFCI p = 0.003; IGR p = 0.006). At DFCI, 5 samples had PD-L1 positive TC (2 mixed GCT, 2 pure choriocarcinomas (CC) and 1 S); at IGR, 14 had positive TC (all NS, including 11 pure CC). More PD-L1 positive TC were CC than other GCT types (DFCI p = 0.003; IGR p < 0.001). In 36 S orchiectomy samples at DFCI, 0/4 that scored none-mild died and 2/31 (6.5%) that scored mod-high died (p = 1.00); in 30 NS orchiectomy samples, 4/9 (44.4%) that scored none-mild died and 2/16 (12.5%) that scored mod-high died (p = 0.14). Conclusions: Higher PD-L1 status in orchiectomy is not associated with GCT survival. PD-L1 positive TC may serve as a histological marker for CC among NS. Higher PD-L1 expression on IC in S and on TC in CC may point to immunotherapy as a therapeutic option in these tumors.

scholarly journals Prognostic value of lymph node evaluation in small bowel adenocarcinoma

Cancer ◽  
2010 ◽  
Vol 116 (23) ◽  
pp. 5374-5382 ◽  
Author(s):  
Michael J. Overman ◽  
Chung-Yuan Hu ◽  
Robert A. Wolff ◽  
George J. Chang
Keyword(s):  
Lymph Node ◽  
Small Bowel ◽  
Prognostic Value ◽  
Small Bowel Adenocarcinoma ◽  
Lymph Node Evaluation

A comparative study of PD-L1 IHC assays using immune cell scoring and CPS in breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15262-e15262
Author(s):  
Bin Li ◽  
Lloye M. Dillon ◽  
Jennifer Jones ◽  
Keyur Desai ◽  
David Gold ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Tumor Grade ◽  
Clear Trend ◽  
Hormone Receptor Positive ◽  
Programmed Death ◽  
Scoring Algorithm ◽  
Formalin Fixed Paraffin Embedded ◽  
Scoring Algorithms

e15262 Background: The clinical benefit of immune checkpoint inhibitors (ICIs) targeting the programmed death-1/programmed death ligand 1 (PD-L1) pathway has previously been demonstrated across a range of tumor types, including in PD-L1+ patients with metastatic triple-negative breast cancer (TNBC). Various PD-L1 immunohistochemistry (IHC) assays and scoring algorithms are being investigated to select patients with breast cancer (BC) most likely to respond to ICIs. Scoring algorithms include PD-L1 expression on tumor cells, immune cells (ICs), or both. We compared the analytical concordance of 3 PD-L1 IHC assays and evaluated PD-L1+ prevalence, using combined positive score (CPS) and % IC scoring algorithms in commercially procured TNBC and hormone receptor–positive, HER2-negative (HR+/HER2−) BC samples. Methods: PD-L1 expression was assessed by HistoGeneX (Naperville, IL) in 163 commercially procured, surgically resected, formalin-fixed, paraffin-embedded BC samples (mostly stage I–III) using the Ventana PD-L1 (SP142) and Dako PD-L1 IHC 28-8 and 22C3 pharmDx assays in conjunction with the CPS (28-8 and 22C3 assays) and % IC algorithms (SP142 and 28-8 assays). PD-L1+ prevalence with each assay and concordance between assays were calculated using CPS ≥ 1 and IC ≥ 1% cutoffs, with a single pathologist assigned to each scoring algorithm. Results: 93 HR+/HER2− BC and 70 TNBC samples were evaluable for PD-L1 expression across all assays and algorithms. Overall concordance was higher between the 28-8 and 22C3 assays (CPS cutoff of 1) than between the 28-8 and SP142 assays (IC cutoff of 1%). PD-L1+ prevalence was similar with the 28-8 and 22C3 assays (CPS ≥ 1) and higher with the 28-8 assay (IC ≥ 1%) than with the SP142 assay (IC ≥ 1%). PD-L1+ samples identified by the SP142 assay (IC ≥ 1%) were mostly included within PD-L1+ sample sets defined by the 28-8 assay (IC ≥ 1% and CPS ≥ 1). PD-L1+ prevalence was higher in TNBC vs HR+/HER2− BC for all assays (Table). No clear trend in PD-L1+ prevalence was observed across tumor grade and stage. Conclusions: High analytical concordance was observed between the 28-8 and 22C3 assays (CPS cutoff of 1) in both HR+/HER2− BC and TNBC samples. PD-L1+ prevalence varied according to IHC assay, scoring algorithm, and cutoff used. Further studies are needed to select the most appropriate PD-L1 assay and scoring algorithm for BC clinical trials. [Table: see text]

scholarly journals Characterization of the Tumor Immune Microenvironment Identifies M0 Macrophage-Enriched Cluster as a Poor Prognostic Factor in Hepatocellular Carcinoma

2020 ◽  
pp. 1002-1013
Author(s):  
Mark Farha ◽  
Neil K. Jairath ◽  
Theodore S. Lawrence ◽  
Issam El Naqa
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Immune Cell ◽  
Multivariable Analysis ◽  
Immune Microenvironment ◽  
Poor Prognostic Factor ◽  
Kaplan Meier ◽  
Programmed Death ◽  
Tumor Immune Microenvironment

PURPOSE Hepatocellular carcinoma (HCC) is characterized by a poor prognosis and a high recurrence rate. The tumor immune microenvironment in HCC has been characterized as shifted toward immunosuppression. We conducted a genomic data-driven classification of immune microenvironment HCC subtypes. In addition, we demonstrated their prognostic value and suggested a potential therapeutic targeting strategy. METHODS RNA sequencing data from The Cancer Genome Atlas–Liver Hepatocellular Carcinoma was used (n = 366). Abundance of immune cells was imputed using CIBERSORT and visualized using unsupervised hierarchic clustering. Overall survival (OS) was analyzed using Kaplan-Meier estimates and Cox regression. Differential expression and gene set enrichment analyses were conducted on immune clusters with poor OS and high programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) coexpression. A scoring metric combining differentially expressed genes and immune cell content was created, and its prognostic value and immune checkpoint blockade response prediction was evaluated. RESULTS Two clusters were characterized by macrophage enrichment, with distinct M0Hi and M2Hi subtypes. M2Hi ( P = .038) and M0Hi ( P = .018) were independently prognostic for OS on multivariable analysis. Kaplan-Meier estimates demonstrated that patients in M0Hi and M2Hi treated with sorafenib had decreased OS ( P = .041), and angiogenesis hallmark genes were enriched in the M0Hi group. CXCL6 and POSTN were overexpressed in both the M0Hi and the PD-1Hi/PD-L1Hi groups. A score consisting of CXCL6 and POSTN expression and absolute M0 macrophage content was discriminatory for OS (intermediate: hazard ratio [HR], 1.59; P ≤ .001; unfavorable: HR, 2.08; P = .04). CONCLUSION Distinct immune cell clusters with macrophage predominance characterize an aggressive HCC phenotype, defined molecularly by angiogenic gene enrichment and clinically by poor prognosis and sorafenib response. This novel immunogenomic signature may aid in stratification of unresectable patients to receive checkpoint inhibitor and antiangiogenic therapy combinations.

Characterization of Immune Cell Infiltration Into Canine Intracranial Meningiomas

2011 ◽  
Vol 49 (5) ◽  
pp. 784-795 ◽  
Author(s):  
L. B. Boozer ◽  
T. W. Davis ◽  
L. B. Borst ◽  
K. M. Zseltvay ◽  
N. J. Olby ◽  
...  
Keyword(s):  
Immune Cell ◽  
Inflammatory Cells ◽  
Cell Infiltration ◽  
Small Subset ◽  
Immune Cell Infiltration ◽  
Prognostic Information ◽  
Intracranial Meningiomas ◽  
Large Numbers ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded

Meningiomas are the most common intracranial tumors in dogs. A variety of inflammatory cells have been shown to invade these tumors in people, but little is known about interactions between the immune system and naturally occurring brain tumors in dogs. The purpose of this study was to investigate the presence of a variety of immune cell subsets within canine intracranial meningiomas. Twenty-three formalin-fixed, paraffin-embedded tumor samples were evaluated using immunohistochemistry with antibodies specific for CD3, CD79a, CD18, CD11d (αD), CD45RA, forkhead box P3, and Toll-like receptors 4 and 9. Immune cell infiltration was evident in all samples, with a predominance of CD3+ T cells. Large numbers of CD18+ microglia and macrophages were noted surrounding and infiltrating the tumors, and a subset of these cells within the tumor appeared to be CD11d+. Scattered macrophages at the tumor–brain interface were TLR4+ and TLR9+. Rare CD79a+ B cells were noted in only a small subset of tumors. Lesser numbers of lymphocytes that were CD11d+, CD45RA+, or FoxP3+ were noted in a number of the meningiomas. Although the function of these cells is not yet clear, work in other species suggests that evaluation of this immune cell infiltrate may provide important prognostic information and may be useful in the design of novel therapies.

scholarly journals Immune Contexture of MMR-Proficient Primary Colorectal Cancer and Matched Liver and Lung Metastases

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1530
Author(s):  
Maarit Ahtiainen ◽  
Hanna Elomaa ◽  
Juha P. Väyrynen ◽  
Erkki-Ville Wirta ◽  
Teijo Kuopio ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Immune Cell ◽  
Lung Metastases ◽  
Primary Tumour ◽  
Treatment Strategies ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Independent Prognostic Marker ◽  
Programmed Death ◽  
Immune Contexture

Purpose: To evaluate immune cell infiltration, the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) expression and their prognostic value in a series of mismatch proficient (pMMR) CRC with matched liver and lung metastases. Methods: Formalin-fixed paraffin-embedded tissue sections stained for CD3, CD8, PD-L1 and PD-1 from 113 primary CRC tumours with 105 liver and 59 lung metastases were analyzed. The amount of CD3 and CD8 positive lymphocytes were combined as immune cell score (ICS). Comparative analyses on immune contexture were performed both between the primary tumour and matched metastases and between the metastatic sites. Results: In liver metastases, immune cell infiltration was increased in general compared to primary tumours but did not correlate case by case. On the contrary, ICS between lung metastases and primary tumours correlated well, but the expression of PD-1/PD-L1 was increased in lung metastases. The proportion of tumours with high ICS together with PD-L1-positivity almost doubled in metastases (39%) compared to primary tumours (20%). High ICS (compared to lowest) in patient’s least immune-infiltrated metastasis was an independent prognostic marker for disease-specific (HR 9.14, 95%CI 2.81–29.68) and overall survival (HR 6.95, 95%CI 2.30–21.00). Conclusions: Our study confirms the prognostic value of high ICS in least immune-infiltrated metastases in pMMR CRC patients. Major differences observed in immune contexture between primary tumours and metastases may have significance for treatment strategies for patients with advanced CRC.

scholarly journals Comprehensive Analysis of SFRP Family Members Prognostic Value and Immune Infiltration in Gastric Cancer

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 522
Author(s):  
Dehua Liu ◽  
Chenyu Sun ◽  
Nahyun Kim ◽  
Chandur Bhan ◽  
John Pocholo Whitaker Tuason ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Prognostic Value ◽  
Immune Cell ◽  
System Development ◽  
Wnt Signaling Pathway ◽  
Immune System Development ◽  
Precision Therapy ◽  
Gastric Cancer Patients

Gastric cancer (GC) is the fifth most common cancer globally. Secreted frizzled-related proteins (SFRP) are important elements associated with the Wnt signaling pathway, and its dysregulated expression is found in multiple cancers. However, the function of distinct SFRPs in GC remains poorly understood. We investigated the differential expression, prognostic value, and immune cell infiltration of SFRPs in gastric cancer patients from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan–Meier plotter, cBioPortal, STRING, Gene-MANIA, DAVID, MethSurv, and TIMER databases. We found that the expression levels of SFRP2 and SFRP4 were significantly increased in GC tissues, whereas the SFRP1 and SFRP5 expressions were reduced. SFRP1, SFRP2, and SFRP5 were significantly correlated with the clinical cancer stage in GC patients. Higher expression of SFRPs was associated with short overall survival (OS) in GC patients. Besides, high SFRPs methylation showed favorable OS in GC patients. The functions of SFRPs were primarily related to the Wnt signaling pathway, immune system development, and basal cell carcinoma. The expression of SFRPs was strongly correlated with immune infiltrating cells, including CD4+ T cells and macrophages in GC. Our study indicated that SFRPs could be potential targets of precision therapy and prognostic biomarkers for the survival of GC patients.

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