Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CMV and EBV targets recognized by tumor-infiltrating B lymphocytes in pancreatic cancer and brain tumors.

ABSTRACT: Targeted antiviral immune responses to the widespread human pathogens cytomegalovirus (CMV) and Epstein-Barr virus (EBV) play a pivotal role in determining immune fitness. We show here for the first time that tumor-infiltrating B cell (TIB)- derived immunoglobulin G (IgG) from patients with pancreatic cancer or glioblastoma have unique anti-CMV/EBV immune recognition patterns compared to serum IgG. There is also great heterogeneity between patients, as well as between serum and TIB-IgG, while some viral targets elicited strongly both T-cell and IgG reactivity in tumor infiltrating T- and B-cells. These observations suggest that the anti-CMV/EBV humoral immune response in situ is highly unique and can be instrumental in developing next-generation immuno-biomarkers in addition to supplementing cellular therapy strategies for personalized cancer therapy targeting CMV or EBV in the tumor microenvironment.

SUBMITTER: Meng Q

PROVIDER: S-EPMC6244284 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

CMV and EBV targets recognized by tumor-infiltrating B lymphocytes in pancreatic cancer and brain tumors.

Meng Qingda Q Valentini Davide D Rao Martin M Dodoo Ernest E Maeurer Markus M

Scientific reports 20181120 1

Targeted antiviral immune responses to the widespread human pathogens cytomegalovirus (CMV) and Epstein-Barr virus (EBV) play a pivotal role in determining immune fitness. We show here for the first time that tumor-infiltrating B cell (TIB)- derived immunoglobulin G (IgG) from patients with pancreatic cancer or glioblastoma have unique anti-CMV/EBV immune recognition patterns compared to serum IgG. There is also great heterogeneity between patients, as well as between serum and TIB-IgG, while so ...[more]

PMID: 30459443

Similar Datasets

Identification of neoepitopes recognized by tumor-infiltrating lymphocytes (TILs) from patients with glioma.

Project description:Neoepitope-specific T-cell responses have been shown to induce durable clinical responses in patients with advanced cancers. We explored the recognition patterns of tumor-infiltrating T lymphocytes (TILs) from patients with glioblastoma multiforme (GBM), the most fatal form of tumors of the central nervous system. Whole-genome sequencing was used for generating DNA sequences representing the entire spectrum of 'private' somatic mutations in GBM tumors from five patients, followed by 15-mer peptide prediction and subsequent peptide synthesis. For each mutated peptide sequence, the wildtype sequence was also synthesized and individually co-cultured with autologous GBM TILs, which had been expanded in vitro with a combination of interleukin (IL)-2, IL-15 and IL-21. After seven days of culture, interferon gamma (IFN-?), tumor necrosis factor alpha (TNF-?) and/or IL-17A production was measured by ELISA in culture supernatants, and used as an epitope-specific immune response readout. Mutated peptides that induced a strong cytokine response were considered to contain legitimate neoepitopes. TILs from 5/5 patients with GBM exhibited specific immune reactivity profiles to the nominal target peptides, defined by IFN-? and/or TNF-? production, as well as IL-17A. Neoepitopes, defined by mutated peptides inducing IFN-? and/or TNF-? production without or only minimal reactivity to the wildtype sequences, were found for each individual patient. CD8+ TILs dominated the patients' responses to private neoepitopes. The present study shows that neoepitope-specific TIL reactivity constitutes an important arm of anti-tumor immune responses in patients with GBM, and thus a powerful tool for developing next-generation personalized immunotherapies.

| S-EPMC5929402 | biostudies-literature

Neoepitope targets of tumour-infiltrating lymphocytes from patients with pancreatic cancer.

Project description:BackgroundPancreatic cancer exhibits a poor prognosis and often presents with metastasis at diagnosis. Immunotherapeutic approaches targeting private cancer mutations (neoantigens) are a clinically viable option to improve clinical outcomes.Methods3/40 TIL lines (PanTT26, PanTT39, PanTT77) were more closely examined for neoantigen recognition. Whole-exome sequencing was performed to identify non-synonymous somatic mutations. Mutant peptides were synthesised and assessed for antigen-specific IFN-γ production and specific tumour killing in a standard Cr51 assay. TIL phenotype was tested by flow cytometry. Lymphocytes and HLA molecules in tumour tissue were visualised by immunohistochemistry.ResultsPanTT26 and PanTT39 TILs recognised and killed the autologous tumour cells. PanTT26 TIL recognised the KRASG12v mutation, while a PanTT39 CD4+ TIL clone recognised the neoepitope (GLLRYWRTERLF) from an aquaporin 1-like protein (gene: K7N7A8). Repeated stimulation of TILs with the autologous tumour cells line lead to focused recognition of several mutated targets, based on IFN-γ production. TILs and corresponding PBMCs from PanTT77 showed shared as well as mutually exclusively tumour epitope recognition (TIL-responsive or PBMC-responsive).ConclusionThis study provides methods to robustly screen T-cell targets for pancreatic cancer. Pancreatic cancer is immunogenic and immunotherapeutic approaches can be used to develop improved, targeted therapies.

| S-EPMC6325142 | biostudies-literature

Imaging Tumor-Infiltrating Lymphocytes in Brain Tumors with [<sup>64</sup>Cu]Cu-NOTA-anti-CD8 PET.

Project description:PurposeGlioblastoma (GBM) is the most common malignant brain tumor in adults. Various immunotherapeutic approaches to improve patient survival are being developed, but the molecular mechanisms of immunotherapy resistance are currently unknown. Here, we explored the ability of a humanized radiolabeled CD8-targeted minibody to noninvasively quantify tumor-infiltrating CD8-positive (CD8+) T cells using PET.Experimental designWe generated a peripheral blood mononuclear cell (PBMC) humanized immune system (HIS) mouse model and quantified the absolute number of CD8+ T cells by flow cytometry relative to the [64Cu]Cu-NOTA-anti-CD8 PET signal. To evaluate a patient-derived orthotopic GBM HIS model, we intracranially injected cells into NOG mice, humanized cohorts with multiple HLA-matched PBMC donors, and quantified CD8+ tumor-infiltrating lymphocytes by IHC. To determine whether [64Cu]Cu-NOTA-anti-CD8 images brain parenchymal T-cell infiltrate in GBM tumors, we performed PET and autoradiography and subsequently stained serial sections of brain tumor tissue by IHC for CD8+ T cells.ResultsNontumor-bearing NOG mice injected with human PBMCs showed prominent [64Cu]Cu-NOTA-anti-CD8 uptake in the spleen and minimal radiotracer localization to the normal brain. NOG mice harboring intracranial human GBMs yielded high-resolution PET images of tumor-infiltrating CD8+ T cells. Radiotracer retention correlated with CD8+ T-cell numbers in spleen and tumor tissue. Our study demonstrates the ability of [64Cu]Cu-NOTA-anti-CD8 PET to quantify peripheral and tumor-infiltrating CD8+ T cells in brain tumors.ConclusionsHuman CD8+ T cells infiltrate an orthotopic GBM in a donor-dependent manner. Furthermore, [64Cu]Cu-NOTA-anti-CD8 quantitatively images both peripheral and brain parenchymal human CD8+ T cells.

| S-EPMC8026513 | biostudies-literature

Prosaposin, tumor-secreted protein, promotes pancreatic cancer progression by decreasing tumor-infiltrating lymphocytes.

Project description:Glycoproteins produced by tumor cells are involved in cancer progression, metastasis, and the immune response, and serve as possible therapeutic targets. Considering the dismal outcomes of pancreatic ductal adenocarcinoma (PDAC) due to its unique tumor microenvironment, which is characterized by low antitumor T-cell infiltration, we hypothesized that tumor-derived glycoproteins may serve as regulating the tumor microenvironment. We used glycoproteomics with tandem mass tag labeling to investigate the culture media of three human PDAC cell lines, and attempted to identify the key secreted proteins from PDAC cells. Among the identified glycoproteins, prosaposin (PSAP) was investigated for its functional contribution to PDAC progression. PSAP is highly expressed in various PDAC cell lines; however, knockdown of intrinsic PSAP expression did not affect the proliferation and migration capacities. Based on the immunohistochemistry of resected human PDAC tissues, high PSAP expression was associated with poor prognosis in patients with PDAC. Notably, tumors with high PSAP expression showed significantly lower CD8+ T-cell infiltration than those with low PSAP expression. Furthermore, PSAP stimulation decreased the proportion of CD8+ T cells in peripheral blood monocytes. Finally, in an orthotopic transplantation model, the number of CD8+ T cells in the PSAP shRNA groups was significantly increased, resulting in a decreased tumor volume compared with that in the control shRNA group. PSAP suppresses CD8+ T-cell infiltration, leading to the promotion of PDAC progression. However, further studies are warranted to determine whether this study contributes to the development of a novel immunomodulating therapy for PDAC.

| S-EPMC9357616 | biostudies-literature

Reliable evaluation of tumor-infiltrating lymphocytes in pancreatic cancer tissue biopsies.

Project description:Tumor-infiltrating lymphocytes (TILs) represent cancer microenvironment. We previously reported TILs was prognosticators in pancreatic ductal adenocarcinoma (PDAC) patients by immunohistochemically measuring them in surgically-resected tissues. The aim of this study was to assess how best to evaluate TILs in PDAC tissue biopsies. First, we showed expression of CD3, CD4, or CD8 genes in PDAC tissue measured by quantitative RT-PCR (RT-qPCR) was prognostic using 241 surgically-resected specimens. We assessed whether the TILs in biopsied tissues can be effectively evaluated by comparing between immunohistochemistry and RT-qPCR. As a study model, we sampled twenty biopsies from surgically-resected PDAC specimen (n = 17). We investigated the variation levels of TILs in the different biopsies from the same specimen and evaluated using the intraclass correlation coefficient (ICC). The ICC value was 0.58 for CD3, 0.61 for CD4, and 0.46 for CD8, respectively; these ICC values meant correlations of "moderate" to "substantial" levels. To reach "near perfect", 3, 3, and 5 times biopsies were necessary for CD3, CD4, and CD8, respectively. When ICC values of immunolabeled TILs were of "low", ≥6 times biopsies were necessary to reach "moderate" levels. We found that TILs measured by RT-qPCR and repeated sampling increased reliability in TILs detected from biopsied PDAC tissues.

| S-EPMC6383689 | biostudies-literature

Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers.

Project description:Immunotherapy with tumor-infiltrating lymphocytes (TIL) or oncolytic adenoviruses, have shown promising results in cancer treatment, when used as separate therapies. When used in combination, the antitumor effect is synergistically potentiated due oncolytic adenovirus infection and its immune stimulating effects on T cells. Indeed, studies in hamsters have shown a 100% complete response rate when animals were treated with oncolytic adenovirus coding for TNFa and IL-2 (Ad5/3-E2F-D24-hTNFa-IRES-hIL2; TILT-123) and TIL therapy. In humans, one caveat with oncolytic virus therapy is that intratumoral injection has been traditionally preferred over systemic administration, for achieving sufficient virus concentrations in tumors, especially when neutralizing antibodies emerge. We have previously shown that 5/3 chimeric oncolytic adenovirus can bind to human lymphocytes for avoidance of neutralization. In this study, we hypothesized that incubation of oncolytic adenovirus (TILT-123) with TILs prior to systemic injection would allow delivery of virus to tumors. This approach would deliver both components in one self-amplifying product. TILs would help deliver TILT-123, whose replication will recruit more TILs and increase their cytotoxicity. In vitro, TILT-123 was seen binding efficiently to lymphocytes, supporting the idea of dual administration. We show in vivo in different models that virus could be delivered to tumors with TILs as carriers.

| S-EPMC8143525 | biostudies-literature

Tumor-infiltrating lymphocytes in melanoma.

Project description:Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) is arguably the most effective treatment for patients with metastatic melanoma. With higher response rates than ipilimumab or IL-2, and longer durations of response than vemurafenib, TIL therapy carries the potential to transform current outcomes in melanoma, while also defining the way cell-based immunotherapy gets incorporated into mainstream cancer treatment. This paper will review the current state of TIL therapy in melanoma, the strategies to improve its efficacy, the current obstacles, and future directions to expand the availability of TIL to the general patient population.

| S-EPMC3462483 | biostudies-literature

Characterization of Immune Cell Subsets of Tumor Infiltrating Lymphocytes in Brain Metastases.

Project description:The heterogeneity of tumor infiltrating lymphocytes (TILs) is not well characterized in brain metastasis. To address this, we performed a targeted analysis of immune-cell subsets in brain metastasis tissues to test immunosuppressive routes involved in brain metastasis. We performed multiplex immunofluorescence (mIF), using commercially available validated antibodies on formalin-fixed paraffin embedded whole sections. We quantitated the subsets of immune-cells utilizing a targeted panel of proteins including PanCK, CD8, CD4, VISTA and IBA-1, and analyzed an average of 15,000 cells per sample. Classifying tumors as either high (>30%) or low (<30%) TILs, we found that increased TILs density correlated with survival. Phenotyping these TILs we found tumors with low TILs had significantly higher expression of the immune-checkpoint molecule VISTA in tumor cells (p < 0.01) as well as in their microenvironment (p < 0.001). Contrastingly, the tumors with high TILs displayed higher levels of microglia, as measured by IBA-1 expression. Low TILs-tumors displayed CD8+ T-cells that co-express VISTA (p < 0.01) significantly more compared to high TILs group, where CD8+cells significantly co-express IBA-11 (p < 0.05). These results were supported by RNA analysis of a publicly available, independent cohort. Our work contributes to a growing understanding of the immune surveillance escape routes active in brain metastasis.

| S-EPMC8150725 | biostudies-literature

Prognostic role of tumor-infiltrating CD57-positive lymphocytes in solid tumors: a meta-analysis.

Project description:The prognostic role of tumor-infiltrating CD57-positive lymphocytes (CD57+ lymphocytes) in human solid tumors remains controversial. Herein, we conducted a meta-analysis including 26 published studies with 7656 patients identified from PubMed and EBSCO to assess the prognostic impact of tumor-infiltrating CD57+ lymphocytes in human solid tumors. We found that CD57+ lymphocyte infiltration significantly improved overall survival (OS) including 1 - year, 3 - year and 5 - year survival, and disease - free survival (DFS) in all types of solid tumors. In stratified analyses, CD57+ lymphocyte infiltration was significantly associated with better OS in hepatocellular, esophageal, head and neck carcinoma, non-small cell lung cancer, 5 - year survival in colorectal cancer, and 3 - year and 5 - year survival in gastric cancer, but not with 1 - year survival in gastric cancer, or 1 - year or 3 - year survival in colorectal cancer. In addition, high density of intratumoral CD57+ lymphocytes was significantly inversely correlated with lymph node metastasis and TNM stage of solid tumor. In conclusion, CD57+ lymphocyte infiltration leads to a favorable clinical outcome in solid tumors, implicating that it is a useful biomarker for prognosis and adoptive immunotherapy based on these cells may be a promising choice for treatment.

| S-EPMC5814286 | biostudies-literature

Comparison of tumor-infiltrating lymphocytes between primary and metastatic tumors in breast cancer patients.

Project description:The presence of tumor-infiltrating lymphocytes (TILs) is associated with favorable long-term outcome in breast cancer. However, little is known about changes in TILs during metastatic progression. To confirm our hypothesis that malignant tumors escape from the host immune system during metastasis, we evaluated the percentage of TILs in paired samples of primary and metastatic breast tumors. We retrospectively identified 25 patients with human epidermal growth factor receptor-2 (HER2+ , n = 14) and triple negative (TN, n = 11) early breast cancer diagnosed between 1990 and 2009 at Tokai University Hospital (Isehara, Japan) and who subsequently experienced regional or distant recurrence confirmed by tumor biopsy/resection. Hematoxylin-eosin-stained slides of these paired samples were evaluated for stromal TILs. Immunohistochemical staining was carried out using primary antibodies against CD4, CD8, Foxp3, programmed cell death ligand 1 (PD-L1), PD-L2, and HLA class I for characterizing the TILs and breast tumors. The percentage of TILs in the primary tumors was significantly higher (average 34.6%) than that in metastatic tumors (average 15.7%) (paired t-test, P = 0.004) and that of CD8+ and CD4+ T cells significantly decreased from primary to metastatic tumors (paired t-test, P = 0.008 and P = 0.026, respectively). The PD-L1, PD-L2, and HLA class I antibody expression changed from positive to negative and vice versa from the primary to the metastatic tumors. Tumors at first metastatic recurrence in HER2+ and TN breast cancers have a lower percentage of TILs and CD8+ and CD4+ T cells compared to primary tumors, which indicates that immune escape plays a role in tumor progression.

| S-EPMC5198965 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data