Case Report: Immune Modulation after PD-1 Inhibitor Therapy in a Patient with Extranodal NK/T-cell Lymphoma Secondary to Chronic Active Epstein-Barr Virus Disease Unveiled by Single-Cell Transcriptomics
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE228279 | GEO | 2023/04/30
REPOSITORIES: GEO
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Project description:Chronic active Epstein-Barr virus disease (CAEBV) is a systemic lymphoproliferative disorder that is closely linked to Epstein-Barr virus (EBV) infection. The clinical course and severity of CAEBV can vary, and in some cases, it can progress to overt lymphoma, which is characterized by extranodal natural killer/T-cell lymphoma (ENKTL) and has a poor clinical outcome. Although anti-programmed cell death protein-1 (PD-1) therapy has shown effectiveness in some patients with EBV-associated disease, it has been less successful in others, and the exact mechanism of action of PD-1 inhibitor therapy in these diseases remains unclear. In this report, we describe a patient who was diagnosed with ENKTL secondary to CAEBV and experienced rapid disease progression accompanied by hyperinflammation after receiving PD-1 inhibitor therapy. Single-cell RNA sequencing revealed a significant increase in the patient's lymphocyte count, especially in natural killer cells, with increased activity following PD-1 inhibitor therapy. This case raises questions about the efficacy and safety of PD-1 inhibitor therapy in patients with EBV-associated diseases.
| S-EPMC10149821 | biostudies-literature
Project description:A 74-year-old woman developed bilateral uveitis with high Epstein-Barr virus (EBV) DNA load in the vitreous fluid without lymphoma cells. Four years after the onset, T2-weighted contrast-enhanced MRI revealed hyperintense lesions in the right occipital and parietal lobe. A biopsy resulted in the diagnosis of extranodal NK/T-cell lymphoma nasal type (ENKL). The repeat region of LMP1, an EBV gene, detected in the brain lesion was identical to that detected in the vitreous fluid. ENKL of the central nervous system is quite rare, and the pathogenesis has not been determined. The lymphoma in this case might have been closely associated with the EBV-positive uveitis.
| S-EPMC5498208 | biostudies-literature
Project description:Tumor-Infiltrating Lymphocytes (TILs) are composed by several immune subpopulations including NK, NKT, Tab, Tgd and B cells. Although some of these cells can have antitumoral activities, there is also a large number of cells which are not tumor-specific,known as bystander cells. These cells may not have a direct role in the antitumoral response but could lead to a modulation of the immune response after time. Recent studies have described fatal encephalitis and myocarditis in cancer patients after immune checkpoint therapies, in which EBV-specific T cells may be involved. Since EBV is able to infect B cells and epithelial cells, both present in the primary tumor site, the first events of these fatal responses could be a consequence of a dysregulation of the immune system in the tumor microenvironment, although this have not been deeply studied. Thus, the main objectives of this study are (i) to use EBV-transformed B cells from the tumor site as a model to study the tumor-infiltrating EBV+ B cells and (ii) to use these EBV-derived B cells to study the relationship with autologous T cells isolated from the tumor site. T cells from TILs have been isolated from a triple negative breast cancer patient before neoadjuvancy and were expanded directly from the biopsy. A Patient-Derived Xenograft (PDX) generated from the breast tumor, progressed into a lymphocytic neoplasm. EBVtransformed B cells were obtained from this PDX (PDX-derived B cells). T Cell Receptor high-throughput sequencing has been used to monitor the clonotypes present in the different samples. We have found 43 clonotypes infiltrating the PDX-562 tissue and 18 of them were also present in the human biopsy or in the biopsy-derived T cell cultures. 5 of these sequences were found in one of the biopsy-derived T cells analyzed. Thus, PDXderived B cells have been used as antigen presenting cells to expand these cells. Few clonotypes were obtained after expansions, although the analysis of the middle CDR3 have revealed a similar pattern with the 18 sequences from the PDX sample. Furthermore, peptides presented by HLA have been eluted from PDX-derived B cells, followed by MS analysis. Peptides obtained derived from 31 different proteins and >40% are cancerrelated in terms of expression.
2021-11-17 | PXD028646 | Pride
Project description:BackgroundExtranodal natural killer T cell lymphoma (ENKTL) is a rare subtype of non-Hodgkin lymphoma with invariable infection of lymphoma cells with Epstein-Barr virus (EBV), and the presence of EBV-DNA in the blood is a well-known prognosticator. However, there is no consensus on which blood compartment is more optimal for predicting survival outcomes.MethodsWe analyzed 60 patients who were newly diagnosed with ENKTL from a prospectively collected database. EBV-DNA was measured in the whole-blood (WB) and plasma at the time of diagnosis and after treatment completion.ResultsEBV-DNA was detected in pre-treatment WB and plasma in 37 (61.7%) and 23 (38.3%) patients, respectively. The presence of pre-treatment plasma EBV-DNA was significantly associated with advanced stage while presence of WB EBV-DNA did not. Positivity of pre-treatment plasma-EBV, but not WB EBV-DNA, was independently associated with poor PFS (HR, 4.22;95% CI, 1.79-9.97; P=0.001) and OS (HR, 8.38; 95% CI, 3.03-23.19; P<0.001) in the multivariate analysis. After treatment completion, positivity of plasma-EBV was independently associated with poor PFS (HR, 9.41; 95% CI, 2.27-39.02; P=0.002) and OS (HR, 32.38; 95% CI, 3.25-322.56; P=0.003), whereas no significant association was observed between WB-EBV status and survival outcomes.ConclusionsOur results suggest that EBV-DNA in the plasma has better prognostic values than WB in patients with ENKTL.
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Project description:Case Report: Immune Modulation after PD-1 Inhibitor Therapy in a Patient with Extranodal NK/T-cell Lymphoma Secondary to Chronic Active Epstein-Barr Virus Disease Unveiled by Single-Cell Transcriptomics
| PRJNA949192 | ENA
Project description:The main target cells for Epstein-Barr virus (EBV) infection and persistence are B lymphocytes, although T and NK cells can also become infected. In this paper, we characterize the EBV present in 21 pediatric and adult patients who were treated in France for a range of diseases that involve infection of T or NK cells. Of these 21 cases, 5 pediatric patients (21%) and 11 adult patients (52%) were of Caucasian origin. In about 30% of the cases, some of the EBV genomes contain a large deletion. The deletions are different in every patient but tend to cluster near the BART region of the viral genome. Detailed investigation of a family in which several members have persistent T or NK cell infection by EBV indicates that the virus genome deletions arise or are selected independently in each individual patient. Genome sequence polymorphisms in the EBV in these T or NK cell diseases reflect the geographic origin of the patient and not a distinct type of EBV (the 21 cases studied included examples of both type 1 and type 2 EBV infection). Using virus produced from type 1 or type 2 EBV genomes cloned in bacterial artificial chromosome (BAC) vectors, we demonstrate infection of T cells in cord blood from healthy donors. Our results are consistent with transient infection of some T cells being part of normal asymptomatic infection by EBV in young children. IMPORTANCE EBV contributes to several types of human cancer. Some cancers and nonmalignant lymphoproliferative diseases involving T or NK cells contain EBV. These diseases are relatively frequent in Japan and China and have been shown sometimes to have deletions in the EBV genome in the disease cells. We identify further examples of deletions within the EBV genome associated with T or NK cell diseases, and we provide evidence that the virus genomes with these deletions are most likely selected in the individual cases, rather than being transmitted between people during infection. We demonstrate EBV infection of cord blood T cells by highly characterized, cloned EBV genomes and suggest that transient infection of T cells may be part of normal asymptomatic infection by EBV in young children.
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Project description:Advanced intrahepatic cholangiocarcinoma (ICC) is a rare malignant tumor of biliary epithelial cells, known for its extremely unfavorable prognosis. In the absence of intervention, patients typically survive for less than 5 months. Current guidelines from the Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN), and European Society for Medical Oncology (ESMO) recommend chemotherapy-based systemic therapy as the standard treatment for advanced ICC. However, the first-line regimen, consisting of gemcitabine in combination with cisplatin, generally results in a median survival of approximately one year, which is considered suboptimal. Significant progress has been made in radiotherapy techniques, molecular diagnostics, and tumor immune microenvironments. The integration of immune and radiation therapies has revolutionized treatment strategies for cholangiocarcinoma. Moreover, combined therapeutic regimens have shown promising results in improving survival rates among patients with advanced ICC. In this study, we present a case report of a 70-year-old male patient diagnosed with stage IV ICC, featuring metastases to the retroperitoneal, left adrenal, and left supraclavicular lymph nodes. The patient exhibited a high tumor mutational load, significant microsatellite instability, and hyper-expression of PD-L1 (90%), along with positive Epstein-Barr virus-encoded RNA (EBER). Pembrolizumab, a programmed cell death 1 (PD-1) inhibitor, was administered in conjunction with radiotherapy. As a result, considerable shrinkage and inactivation of the primary foci were observed, accompanied by the disappearance of metastases. Ultimately, the patient achieved complete remission and maintained progression-free survival for 41 months following the initial treatment. To the best of our knowledge, this represents the longest case of complete remission using a combination of immunotherapy and radiotherapy as a first-line regimen for the high tumor mutational load, microsatellite instability, and PD-L1 expression (90%) subtype of Epstein-Barr virus-associated ICC (EBVaICC). These findings suggest that the combination of PD-1 inhibitors with radiotherapy may serve as a promising therapeutic strategy for treating this particular cancer subtype.
| S-EPMC10518395 | biostudies-literature
Project description:Chronic lymphocytic leukemia often results in secondary tumors, the most common being large B cell lymphoma known as Richter syndrome, followed by extranodal NK/T-cell lymphoma (nasal type) is extremely rare.A chronic lymphocytic leukemia patient presented with nasal congestion.Nasal endoscopy identified a left nasal mass, and the pathology suggested extranodal NK/T-cell lymphoma (nasal type).The patient received a course of chemotherapy.Pneumonia and coagulopathy occurred after chemotherapy, and the patient died shortly thereafter.It is essential to recognize the transformation of disease earlier in chronic lymphoblastic leukemia patient.
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Project description:Hemophagocytic lymphohistiocytosis (HLH) is rare and life threatening syndrome. There are only a few reported cases of HLH with GI symptoms. We describe the case of an 18 months old boy who presented with a history of fever for 40 days, abdominal distention and hepatosplenomegaly. Abdominal x-ray showed a pneumoperitoneum. Urgent laparotomy was done which revealed an isolated cecal perforation. The histopathological findings in the subsequent resected bowel was HLH with evidence of positive EBV Barr infection.
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Project description:EBV-specific T cells have been recently described to be involved in fatal encephalitis and myocarditis in cancer patients after immune checkpoint therapies. Here, we report the study of a human triple-negative breast cancer tumor (TNBC) and EBV-transformed B cells obtained from a patient-derived xenograft (PDX) that progressed into a lymphocytic neoplasm named xenograft-associated B-cell lymphoma (XABCL). T-cell receptor (TCR) high-throughput sequencing was performed to monitor the T-cell clonotypes present in the different samples. Forty-three T-cell clonotypes were found infiltrating the XABCL tissue after three passes in mice along 6 months. Eighteen of these (42%) were also found in the TNBC biopsy. TCR infiltrating the XABCL tissue showed a very restricted T-cell repertoire as compared with the biopsy-infiltrating T cells. Consequently, T cells derived from the TNBC biopsy were expanded in the presence of the B-cell line obtained from the XABCL (XABCL-LCL), after which the TCR repertoire obtained was again very restricted, i.e., only certain clonotypes were selected by the B cells. A number of these TCRs had previously been reported as sequences involved in infection, cancer, and/or autoimmunity. We then analyzed the immunopeptidome from the XABCL-LCL, to identify putative B-cell-associated peptides that might have been expanding these T cells. The HLA class I and class II-associated peptides from XABCL-LCL were then compared with published repertoires from LCL of different HLA typing. Proteins from the antigen processing and presentation pathway remained significantly enriched in the XABCL-LCL repertoire. Interestingly, some class II-presented peptides were derived from cancer-related proteins. These results suggest that bystander tumor-infiltrating EBV+ B cells acting as APC may be able to interact with tumor-infiltrating T cells and influence the TCR repertoire in the tumor site.
| S-EPMC8637110 | biostudies-literature