LIVIVO - Search results -

Search results

Result 1 - 10 of total 37

Search options

Article: Microenvironmental immune cell alterations across the spectrum of nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma.

Panayi, Christos / Akarca, Ayse U / Ramsay, Alan D / Shankar, Ananth G / Falini, Brunangelo / Piris, Miguel A / Linch, David / Marafioti, Teresa

Frontiers in oncology

2023 Volume 13, Page(s) 1267604

Abstract: Background: The clinicopathological spectrum of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), also known as nodular lymphocyte predominant B-cell lymphoma, partially overlaps with T-cell/histiocyte-rich large B-cell lymphoma (THRLCBL). NLPHL ... ...

Abstract	Background: The clinicopathological spectrum of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), also known as nodular lymphocyte predominant B-cell lymphoma, partially overlaps with T-cell/histiocyte-rich large B-cell lymphoma (THRLCBL). NLPHL histology may vary in architecture and B-cell/T-cell composition of the tumour microenvironment. However, the immune cell phenotypes accompanying different histological patterns remain poorly characterised. Methods: We applied a multiplexed immunofluorescence workflow to identify differential expansion/depletion of multiple microenvironmental immune cell phenotypes between cases of NLPHL showing different histological patterns (as described by Fan et al, 2003) and cases of THRLBCL. Results: FOXP3-expressing T-regulatory cells were conspicuously depleted across all NLPHL cases. As histology progressed to variant Fan patterns C and E of NLPHL and to THRLBCL, there were progressive expansions of cytotoxic granzyme-B-expressing natural killer and CD8-positive T-cells, PD1-expressing CD8-positive T-cells, and CD163-positive macrophages including a PDL1-expressing subset. These occurred in parallel to depletion of NKG2A-expressing natural killer and CD8-positive T-cells. Discussion: These findings provide new insights on the immunoregulatory mechanisms involved in NLPHL and THLRBCL pathogenesis, and are supportive of an increasingly proposed biological continuum between these two lymphomas. Additionally, the findings may help establish new biomarkers of high-risk disease, which could support a novel therapeutic program of immune checkpoint interruption targeting the PD1:PDL1 and/or NKG2A:HLA-E axes in the management of high-risk NLPHL and THRLBCL.
Language	English
Publishing date	2023-10-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1267604
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Self-supervised deep learning for highly efficient spatial immunophenotyping.

Zhang, Hanyun / AbdulJabbar, Khalid / Grunewald, Tami / Akarca, Ayse U / Hagos, Yeman / Sobhani, Faranak / Lecat, Catherine S Y / Patel, Dominic / Lee, Lydia / Rodriguez-Justo, Manuel / Yong, Kwee / Ledermann, Jonathan A / Le Quesne, John / Hwang, E Shelley / Marafioti, Teresa / Yuan, Yinyin

EBioMedicine

2023 Volume 95, Page(s) 104769

Abstract: Background: Efficient biomarker discovery and clinical translation depend on the fast and accurate analytical output from crucial technologies such as multiplex imaging. However, reliable cell classification often requires extensive annotations. Label- ... ...

Abstract	Background: Efficient biomarker discovery and clinical translation depend on the fast and accurate analytical output from crucial technologies such as multiplex imaging. However, reliable cell classification often requires extensive annotations. Label-efficient strategies are urgently needed to reveal diverse cell distribution and spatial interactions in large-scale multiplex datasets. Methods: This study proposed Self-supervised Learning for Antigen Detection (SANDI) for accurate cell phenotyping while mitigating the annotation burden. The model first learns intrinsic pairwise similarities in unlabelled cell images, followed by a classification step to map learnt features to cell labels using a small set of annotated references. We acquired four multiplex immunohistochemistry datasets and one imaging mass cytometry dataset, comprising 2825 to 15,258 single-cell images to train and test the model. Findings: With 1% annotations (18-114 cells), SANDI achieved weighted F1-scores ranging from 0.82 to 0.98 across the five datasets, which was comparable to the fully supervised classifier trained on 1828-11,459 annotated cells (-0.002 to -0.053 of averaged weighted F1-score, Wilcoxon rank-sum test, P = 0.31). Leveraging the immune checkpoint markers stained in ovarian cancer slides, SANDI-based cell identification reveals spatial expulsion between PD1-expressing T helper cells and T regulatory cells, suggesting an interplay between PD1 expression and T regulatory cell-mediated immunosuppression. Interpretation: By striking a fine balance between minimal expert guidance and the power of deep learning to learn similarity within abundant data, SANDI presents new opportunities for efficient, large-scale learning for histology multiplex imaging data. Funding: This study was funded by the Royal Marsden/ICR National Institute of Health Research Biomedical Research Centre.
MeSH term(s)	Humans ; Female ; Immunophenotyping ; Deep Learning ; Biomedical Research ; Immunosuppression Therapy ; Ovarian Neoplasms
Language	English
Publishing date	2023-09-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2023.104769
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 7090: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: CD47 expression in acute myeloid leukemia varies according to genotype.

Marra, Andrea / Akarca, Ayse U / Martino, Giovanni / Ramsay, Alan / Ascani, Stefano / Perriello, Vincenzo Maria / O'Nions, Jenny / Wilson, Andrew J / Gupta, Rajeev / Childerhouse, Anna / Proctor, Ian / Rodriguez-Justo, Manuel / Pomplun, Sabine / Martelli, Maria Paola / Lo Celso, Cristina / Falini, Brunangelo / Marafioti, Teresa

Haematologica

2023 Volume 108, Issue 12, Page(s) 3491–3495

MeSH term(s)	Humans ; CD47 Antigen/genetics ; CD47 Antigen/metabolism ; Leukemia, Myeloid, Acute/diagnosis ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/metabolism ; Antibodies, Monoclonal ; Genotype
Chemical Substances	CD47 Antigen ; Antibodies, Monoclonal ; CD47 protein, human
Language	English
Publishing date	2023-12-01
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2023.283154
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.76: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Phenotyping of lymphoproliferative tumours generated in xenografts of non-small cell lung cancer.

Pearce, David R / Akarca, Ayse U / De Maeyer, Roel P H / Kostina, Emily / Huebner, Ariana / Sivakumar, Monica / Karasaki, Takahiro / Shah, Kavina / Janes, Sam M / McGranahan, Nicholas / Reddy, Venkat / Akbar, Arne N / Moore, David A / Marafioti, Teresa / Swanton, Charles / Hynds, Robert E

Frontiers in oncology

2023 Volume 13, Page(s) 1156743

Abstract: Background: Patient-derived xenograft (PDX) models involve the engraftment of tumour tissue in immunocompromised mice and represent an important pre-clinical oncology research method. A limitation of non-small cell lung cancer (NSCLC) PDX model ... ...

Abstract	Background: Patient-derived xenograft (PDX) models involve the engraftment of tumour tissue in immunocompromised mice and represent an important pre-clinical oncology research method. A limitation of non-small cell lung cancer (NSCLC) PDX model derivation in NOD- Methods: The immunophenotype of lymphoproliferations arising in the lung TRACERx PDX pipeline were characterised. To present the histology data herein, we developed a Python-based tool for generating patient-level pathology overview figures from whole-slide image files; PATHOverview is available on GitHub (https://github.com/EpiCENTR-Lab/PATHOverview). Results: Lymphoproliferations occurred in 17.8% of lung adenocarcinoma and 10% of lung squamous cell carcinoma transplantations, despite none of these patients having a prior or subsequent clinical history of lymphoproliferative disease. Lymphoproliferations were predominantly human CD20+ B cells and had the immunophenotype expected for post-transplantation diffuse large B cell lymphoma with plasma cell features. All lymphoproliferations expressed Epstein-Barr-encoded RNAs (EBER). Analysis of immunoglobulin light chain gene rearrangements in three tumours where multiple tumour regions had resulted in lymphoproliferations suggested that each had independent clonal origins. Discussion: Overall, these data suggest that B cell clones with lymphoproliferative potential are present within primary NSCLC tumours, and that these are under continuous immune surveillance. Since these cells can be expanded following transplantation into NSG mice, our data highlight the value of quality control measures to identify lymphoproliferations within xenograft pipelines and support the incorporation of strategies to minimise lymphoproliferations during the early stages of xenograft establishment pipelines.
Language	English
Publishing date	2023-06-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1156743
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: High inter-follicular spatial co-localization of CD8+FOXP3+ with CD4+CD8+ cells predicts favorable outcome in follicular lymphoma.

Hagos, Yeman B / Akarca, Ayse U / Ramsay, Alan / Rossi, Riccardo L / Pomplun, Sabine / Ngai, Victoria / Moioli, Alessia / Gianatti, Andrea / Mcnamara, Christopher / Rambaldi, Alessandro / Quezada, Sergio A / Linch, David / Gritti, Giuseppe / Yuan, Yinyin / Marafioti, Teresa

Hematological oncology

2022 Volume 40, Issue 4, Page(s) 541–553

Abstract: The spatial architecture of the lymphoid tissue in follicular lymphoma (FL) presents unique challenges to studying its immune microenvironment. We investigated the spatial interplay of T cells, macrophages, myeloid cells and natural killer T cells using ... ...

Abstract	The spatial architecture of the lymphoid tissue in follicular lymphoma (FL) presents unique challenges to studying its immune microenvironment. We investigated the spatial interplay of T cells, macrophages, myeloid cells and natural killer T cells using multispectral immunofluorescence images of diagnostic biopsies of 32 patients. A deep learning-based image analysis pipeline was tailored to the needs of follicular lymphoma spatial histology research, enabling the identification of different immune cells within and outside neoplastic follicles. We analyzed the density and spatial co-localization of immune cells in the inter-follicular and intra-follicular regions of follicular lymphoma. Low inter-follicular density of CD8+FOXP3+ cells and co-localization of CD8+FOXP3+ with CD4+CD8+ cells were significantly associated with relapse (p = 0.0057 and p = 0.0019, respectively) and shorter time to progression after first-line treatment (Logrank p = 0.0097 and log-rank p = 0.0093, respectively). A low inter-follicular density of CD8+FOXP3+ cells is associated with increased risk of relapse independent of follicular lymphoma international prognostic index (FLIPI) (p = 0.038, Hazard ratio (HR) = 0.42 [0.19, 0.95], but not independent of co-localization of CD8+FOXP3+ with CD4+CD8+ cells (p = 0.43). Co-localization of CD8+FOXP3+ with CD4+CD8+ cells is predictors of time to relapse independent of the FLIPI score and density of CD8+FOXP3+ cells (p = 0.027, HR = 0.0019 [7.19 × 10
MeSH term(s)	CD8-Positive T-Lymphocytes ; Forkhead Transcription Factors ; Humans ; Lymphoma, Follicular/pathology ; Neoplasm Recurrence, Local ; Prognosis ; Tumor Microenvironment
Chemical Substances	FOXP3 protein, human ; Forkhead Transcription Factors
Language	English
Publishing date	2022-04-28
Publishing country	England
Document type	Journal Article
ZDB-ID	604884-5
ISSN	1099-1069 ; 0278-0232
ISSN (online)	1099-1069
ISSN	0278-0232
DOI	10.1002/hon.3003
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1816: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Systematic Evaluation of the Immune Environment of Small Intestinal Neuroendocrine Tumors.

Vesely, Clare / Wong, Yien Ning Sophia / Childs, Alexa / Akarca, Ayse U / Dhami, Pawan / Vaikkinen, Heli / Conde, Lucia / Herrero, Javier / Ogunbiyi, Olagunju / Gander, Amir / Luong, Tu Vinh / Thirlwell, Chrissie / Caplin, Martyn / Toumpanakis, Christos / Peggs, Karl / Quezada, Sergio A / Marafioti, Teresa / Meyer, Tim

Clinical cancer research : an official journal of the American Association for Cancer Research

2022 Volume 28, Issue 12, Page(s) 2657–2668

Abstract: Purpose: The immune tumor microenvironment and the potential therapeutic opportunities for immunotherapy in small intestinal neuroendocrine tumors (siNET) have not been fully defined.: Experimental design: Herein, we studied 40 patients with primary ... ...

Abstract	Purpose: The immune tumor microenvironment and the potential therapeutic opportunities for immunotherapy in small intestinal neuroendocrine tumors (siNET) have not been fully defined. Experimental design: Herein, we studied 40 patients with primary and synchronous metastatic siNETs, and matched blood and normal tissue obtained during surgery. We interrogated the immune checkpoint landscape using multi-parametric flow cytometry. In addition, matched FFPE tissue was obtained for multi-parametric IHC to determine the relative abundance and distribution of T-cell infiltrate. Tumor mutational burden (TMB) was also assessed and correlated with immune infiltration. Results: Effector tumor-infiltrating lymphocytes (TIL) had a higher expression of PD-1 in the tumor microenvironment compared with the periphery. In addition, CD8+ TILs had a significantly higher co-expression of PD-1/ICOS and PD-1/CTLA-4 (cytotoxic T lymphocyte antigen-4) and higher levels of PD-1 expression compared with normal tissue. IHC revealed that the majority of cases have ≤10% intra-tumoral T cells but a higher number of peri-tumoral T cells, demonstrating an "exclusion" phenotype. Finally, we confirmed that siNETs have a low TMB compared with other tumor types in the TCGA database but did not find a correlation between TMB and CD8/Treg ratio. Conclusions: Taken together, these results suggest that a combination therapy approach will be required to enhance the immune response, using PD-1 as a checkpoint immunomodulator backbone in combination with other checkpoint targeting molecules (CTLA-4 or ICOS), or with drugs targeting other pathways to recruit "excluded" T cells into the tumor microenvironment to treat patients with siNETs.
MeSH term(s)	Biomarkers, Tumor/metabolism ; CD8-Positive T-Lymphocytes ; CTLA-4 Antigen ; Humans ; Intestinal Neoplasms/pathology ; Lymphocytes, Tumor-Infiltrating ; Neuroendocrine Tumors/pathology ; Programmed Cell Death 1 Receptor ; Tumor Microenvironment/genetics
Chemical Substances	Biomarkers, Tumor ; CTLA-4 Antigen ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2022-03-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-21-4203
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4223: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Transcriptional analysis of multiple ovarian cancer cohorts reveals prognostic and immunomodulatory consequences of ERV expression.

Natoli, Marina / Gallon, John / Lu, Haonan / Amgheib, Ala / Pinato, David J / Mauri, Francesco A / Marafioti, Teresa / Akarca, Ayse U / Ullmo, Ines / Ip, Jacey / Aboagye, Eric O / Brown, Robert / Karadimitris, Anastasios / Ghaem-Maghami, Sadaf

Journal for immunotherapy of cancer

2021 Volume 9, Issue 1

Abstract: Background: Endogenous retroviruses (ERVs) play a role in a variety of biological processes, including embryogenesis and cancer. DNA methyltransferase inhibitors (DNMTi)-induced ERV expression triggers interferon responses in ovarian cancer cells via ... ...

Abstract	Background: Endogenous retroviruses (ERVs) play a role in a variety of biological processes, including embryogenesis and cancer. DNA methyltransferase inhibitors (DNMTi)-induced ERV expression triggers interferon responses in ovarian cancer cells via the viral sensing machinery. Baseline expression of ERVs also occurs in cancer cells, though this process is poorly understood and previously unexplored in epithelial ovarian cancer (EOC). Here, the prognostic and immunomodulatory consequences of baseline ERV expression was assessed in EOC. Methods: ERV expression was assessed using EOC transcriptional data from The Cancer Genome Atlas (TCGA) and from an independent cohort (Hammersmith Hospital, HH), as well as from untreated or DNMTi-treated EOC cell lines. Least absolute shrinkage and selection operator (LASSO) logistic regression defined an ERV expression score to predict patient prognosis. Immunohistochemistry (IHC) was conducted on the HH cohort. Combination of DNMTi treatment with γδ T cells was tested Results: ERV expression was found to define clinically relevant subsets of EOC patients. An ERV prognostic score was successfully generated in TCGA and validated in the independent cohort. In EOC patients from this cohort, a high ERV score was associated with better survival (log-rank p=0.0009) and correlated with infiltration of CD8+PD1+T cells (r=0.46, p=0.0001). In the TCGA dataset, a higher ERV score was found in BRCA1/2 mutant tumors, compared to wild type (p=0.015), while a lower ERV score was found in CCNE1 amplified tumors, compared to wild type (p=0.019). Conclusions: These findings uncover the potential for baseline ERV expression to robustly inform EOC patient prognosis, influence tumor immune infiltration and affect antitumor immunity.
MeSH term(s)	BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Carcinoma, Ovarian Epithelial/drug therapy ; Carcinoma, Ovarian Epithelial/genetics ; Carcinoma, Ovarian Epithelial/immunology ; Cell Line, Tumor ; Cyclin E/genetics ; Decitabine/pharmacology ; Decitabine/therapeutic use ; Endogenous Retroviruses/drug effects ; Female ; Gene Amplification ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic/drug effects ; High-Throughput Nucleotide Sequencing ; Humans ; Intraepithelial Lymphocytes/drug effects ; Intraepithelial Lymphocytes/immunology ; Mutation ; Oncogene Proteins/genetics ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/immunology ; Prognosis ; Sequence Analysis, RNA ; Survival Analysis
Chemical Substances	BRCA1 Protein ; BRCA1 protein, human ; BRCA2 Protein ; BRCA2 protein, human ; CCNE1 protein, human ; Cyclin E ; Oncogene Proteins ; Decitabine (776B62CQ27)
Language	English
Publishing date	2021-01-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2020-001519
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Integrated phenotyping of the anti-cancer immune response in HIV-associated hepatocellular carcinoma.

Pinato, David J / Kaneko, Takahiro / D'Alessio, Antonio / Forner, Alejandro / Fessas, Petros / Minguez, Beatriz / Giannini, Edoardo G / Grillo, Federica / Díaz, Alba / Mauri, Francesco A / Fulgenzi, Claudia A M / Dalla Pria, Alessia / Goldin, Robert D / Pieri, Giulia / Toniutto, Pierluigi / Avellini, Claudio / Plaz Torres, Maria Corina / Akarca, Ayse U / Marafioti, Teresa /

Bhoori, Sherrie / Miró, Jose María / Bower, Mark / Bräu, Norbert / Mazzaferro, Vincenzo

JHEP reports : innovation in hepatology

2023 Volume 5, Issue 7, Page(s) 100741

Abstract: Background & aims: HIV-seropositivity shortens survival in patients with hepatocellular carcinoma (HCC). Although risk factors for HCC including HCV infection can influence T cell phenotype, it is unknown whether HIV can influence functional ... ...

Abstract	Background & aims: HIV-seropositivity shortens survival in patients with hepatocellular carcinoma (HCC). Although risk factors for HCC including HCV infection can influence T cell phenotype, it is unknown whether HIV can influence functional characteristics of the T cell infiltrate. Methods: From the Liver Cancer in HIV biorepository, we derived 129 samples of transplanted (76%) or resected (20%) HCC in eight European and North American centres. We profiled intra- and peritumoural tissue to evaluate regulatory CD4+/FOXP3+ and immune-exhausted CD8+/PD1+ T cells in HIV+ (n = 66) and HIV- (n = 63) samples. We performed targeted transcriptomics and T-cell receptor sequencing in a restricted subset of samples evaluated in relationship with HIV status. We correlated immunopathologic features with patients' characteristics including markers of HIV infection. Results: Of the 66 HIV+ patients, 83% were HCV coinfected with an undetectable HIV viral load (51%) and a median blood CD4+ cell count of 430 cells/mm Conclusions: HIV-associated HCC harbours a profoundly immune-exhausted tumour microenvironment, warranting prospective testing of immunotherapy in this treatment-deprived patient population. Impact and implications: Hepatocellular carcinoma is a non-AIDS defining malignancy characterised by poor survival. The programmed cell death (PD-1) pathway governs antiviral and anticancer immune exhaustion and is a therapeutic target in HCC. This study highlights how HIV infection is associated with significantly higher PD-L1 expression in HCC cells and in the surrounding microenvironment, leading to changes in cytotoxic and regulatory T cell function and dysregulation of proinflammatory pathways. Taken together, our results suggest dysfunctional T cell immunity as a mechanism of worse outcome in these patients and suggest clinical testing of checkpoint inhibitors in HIV-associated HCC.
Language	English
Publishing date	2023-03-22
Publishing country	Netherlands
Document type	Journal Article
ISSN	2589-5559
ISSN (online)	2589-5559
DOI	10.1016/j.jhepr.2023.100741
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Spatial Architecture of Myeloid and T Cells Orchestrates Immune Evasion and Clinical Outcome in Lung Cancer.

Enfield, Katey S S / Colliver, Emma / Lee, Claudia S Y / Magness, Alastair / Moore, David A / Sivakumar, Monica / Grigoriadis, Kristiana / Pich, Oriol / Karasaki, Takahiro / Hobson, Philip S / Levi, Dina / Veeriah, Selvaraju / Puttick, Clare / Nye, Emma L / Green, Mary / Dijkstra, Krijn K / Shimato, Masako / Akarca, Ayse U / Marafioti, Teresa /

Salgado, Roberto / Hackshaw, Allan / Consortium, TRACERx / Jamal-Hanjani, Mariam / van Maldegem, Febe / McGranahan, Nicholas / Glass, Benjamin / Pulaski, Hanna / Walk, Eric / Reading, James L / Quezada, Sergio A / Hiley, Crispin T / Downward, Julian / Sahai, Erik / Swanton, Charles / Angelova, Mihaela

Cancer discovery

2024

Abstract: Understanding the role of the tumour microenvironment (TME) in lung cancer is critical to improving patient outcome. We identified four histology-independent archetype TMEs in treatment-naive early-stage lung cancer using imaging mass cytometry in the ... ...

Abstract	Understanding the role of the tumour microenvironment (TME) in lung cancer is critical to improving patient outcome. We identified four histology-independent archetype TMEs in treatment-naive early-stage lung cancer using imaging mass cytometry in the TRACERx study (n=81 patients/198 samples/2.3million cells). In immune-hot adenocarcinomas, spatial niches of T cells and macrophages increased with clonal neoantigen burden, whereas such an increase was observed for niches of plasma and B cells in immune-excluded squamous cell carcinomas (LUSC). Immune-low TMEs were associated with fibroblast barriers to immune infiltration. The fourth archetype, characterised by sparse lymphocytes and high tumour-associated neutrophil (TAN) infiltration, had tumour cells spatially separated from vasculature and exhibited low spatial intratumour heterogeneity. TAN-High LUSC had frequent PIK3CA mutations. TAN-High tumours harboured recently expanded and metastasis-seeding subclones and had a shorter disease-free survival independent of stage. These findings delineate genomic, immune and physical barriers to immune surveillance and implicate neutrophil-rich TMEs in metastasis.
Language	English
Publishing date	2024-04-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2625242-9
ISSN	2159-8290 ; 2159-8274
ISSN (online)	2159-8290
ISSN	2159-8274
DOI	10.1158/2159-8290.CD-23-1380
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6916: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Megakaryocytes, erythropoietic and granulopoietic cells express CAL2 antibody in myeloproliferative neoplasms carrying CALR gene mutations.

Ali, Hebah / Puccio, Ignazio / Akarca, Ayse U / Bob, Roshanak / Pomplun, Sabine / Keong Wong, Wai / Gupta, Rajeev / Sekhar, Mallika / Lambert, Jonathan / Al-Masri, Hytham / Stein, Harald / Marafioti, Teresa

International journal of experimental pathology

2020 Volume 102, Issue 1, Page(s) 45–50

Abstract: Testing for the CALR mutation is included in the updated WHO criteria for essential thrombocythaemia (ET) and primary myelofibrosis (PMF). We report on the application of the CAL2 monoclonal antibody, raised against the mutated CALR gene to myeloid cases. ...

Abstract	Testing for the CALR mutation is included in the updated WHO criteria for essential thrombocythaemia (ET) and primary myelofibrosis (PMF). We report on the application of the CAL2 monoclonal antibody, raised against the mutated CALR gene to myeloid cases. The immunostain was used on 116 acute myeloid leukaemias (AML) and 66 myeloproliferative neoplasms (MPN) or myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN). None of AML cases was stained by the CAL2 antibody, while 20/66 MPNs and MDS/MPNs appeared positive. Fourteen of the latter cases were studied by molecular techniques, and all showed aberrations of the CALR gene. In addition, CAL2 positivity was found in some small-sized elements besides megakaryocytes. By double staining, these elements corresponded to small megakaryocytes as well as both erythroid and myeloid precursors. This finding suggests possible occurrence of CALR gene abnormalities in a stem cell.
MeSH term(s)	Antibodies, Monoclonal ; Calreticulin/genetics ; Erythrocytes/metabolism ; Granulocytes/metabolism ; Humans ; Megakaryocytes/metabolism ; Mutation ; Myelodysplastic-Myeloproliferative Diseases/diagnosis ; Myelodysplastic-Myeloproliferative Diseases/genetics ; Myeloproliferative Disorders/diagnosis ; Myeloproliferative Disorders/genetics
Chemical Substances	Antibodies, Monoclonal ; CALR protein, human ; Calreticulin
Language	English
Publishing date	2020-09-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1016006-1
ISSN	1365-2613 ; 0958-4625 ; 0007-1021 ; 0959-9673
ISSN (online)	1365-2613
ISSN	0958-4625 ; 0007-1021 ; 0959-9673
DOI	10.1111/iep.12375
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Ud II Zs.52: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

To top

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito