scholarly journals The Prognostic Value of Tumor-Infiltrating Immune Cells in Gynecologic Cancers

2021 ◽  
Author(s):  
Waichung Chen ◽  
Tuo Hu ◽  
Chunbo He
Keyword(s):  
Ovarian Cancer ◽  
Cervical Cancer ◽  
T Cells ◽  
Dendritic Cells ◽  
Cancer Patients ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Uterine Cancer ◽  
Cell Infiltration ◽  
Gynecologic Cancers

AbstractImmunotherapy has changed the standard of treatment for many cancers. However, only a small number of gynecologic cancer patients benefit from immunotherapy. The intra-tumoral immune landscapes are suggested as a predictor of the response to immunotherapies, but there are no studies that provide a comprehensive immune characterization for gynecologic cancers. To characterize cellular compositions of the immune infiltrates and investigate if the immune landscape is a predictor for patient prognosis in gynecologic cancers, we analyzed tumor immune infiltrates of ovarian cancer, cervical cancer, and uterine cancer from The Cancer Genome Atlas Program (TCGA) using QuanTIseq and EPIC. Ovarian cancer had the highest percentage of total immune cells. Cervical cancer and uterine corpus endometrial carcinoma have lower percentages of immune cells with 17% and 16%, respectively. Furthermore, ovarian cancer had a significantly higher monocyte and M2-liked macrophage percentage, but a lower percentage for CD8 T cells and neutrophils compared to cervical cancer and uterine cancer. Cervical cancer had the highest percentage for M1-liked macrophages and the lowest for CD4 T cells. Uterine cancer had the highest percentage of dendritic cells. In cervical cancer, higher cell infiltration of CD8 T-Cells and M2-liked macrophages was associated with a better prognosis. In uterine cancer, patients with a higher number of dendritic cells and CD8 T-Cells had significantly better clinical outcomes. However, higher CD4 T-cell infiltration was associated with a poor prognosis in uterine cancer. Interestingly, the patient survival was not affected by the infiltration of any individual immune cells which we analyzed in ovarian cancer. We identified and validated four immune subtypes associated with distinct immune cell infiltration in gynecologic cancers. Cervical and uterine cancer patients from an immune-desert subtype that had the least amount of lymphocyte infiltration and a high level of monocyte had the worst prognosis. By contrast, cervical and uterine cancer patients from an immune-warm subtype that had higher infiltration of CD8 T-cell, natural killer (NK) cells, and dendritic cells (DCs) had the best prognosis. However, the survival rate of ovarian cancer patients is similar among the four different subtypes. Our study provides a conceptual framework to understand the tumor immune microenvironment of different gynecologic cancers.

scholarly journals ILDR1 Is a Prognostic Biomarker and Associated With Immune Infiltration in Gastric Cancer

2021 ◽  
Author(s):  
Yanling Ma ◽  
WenBo Qi ◽  
BaoHong Gu ◽  
XueMei Li ◽  
ZhenYu Yin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Dendritic Cells ◽  
Cancer Patients ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Copy Number ◽  
Sequencing Data ◽  
Number Variation ◽  
Gastric Cancer Patients

Abstract Objective: To investigate the association between ILDR1 and prognosis and immune infiltration in gastric cancer. Methods: We analyzed the RNA sequencing data of 9736 tumor tissues and 8587 normal tissues in the TCGA and GTEx databases through the GEPIA2 platform. The expression of ILDR1 in gastric cancer and normal gastric mucosa tissues with GEPIA and TIMER. Clinical subgroup analysis was made through Kaplan-Meier analysis. Analyzed the correlation between ILDR1 and VEGFA expression in gastric cancer, through the gene sequencing data of gastric cancer in TCGA. Explored the relationship between ILDR1 methylation and the prognosis of gastric cancer patients through the MethSurv database. The correlation between ILDR1 and immune cells and the correlation of copy number variation were explored through the TIMER database. Results: ILDR1-high GC patients had a lower PFS and OS. High ILDR1 expression was significantly correlated with tumor grade. There was a negative correlation between the ILDR1 expression and the abundances of CD8+ T, Macrophages and DC and etc. The methylation level of ILDR1 is associated with a good prognosis of gastric cancer. ILDR1 copy number variation was correlated with immune cells, IDLR1 arm-loss was associated with the infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells, and arm-duplication was associated with the infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells. Conclusion: The increased expression of ILDR1 is associated with poor prognosis in patients with gastric cancer. ILDR1 can be used as a novel predictive biomarker to provide a new therapeutic target for gastric cancer patients.

scholarly journals High Expression Level of miR-1260 Family in the Peripheral Blood of Patients with Ovarian Carcinoma

2020 ◽  
Author(s):  
Arash Adamnejad Ghafour ◽  
Demet Akdeniz Odemis ◽  
Seref Bugra Tuncer ◽  
Busra Kurt ◽  
Mukaddes Avsar Sarali ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cervical Cancer ◽  
Cancer Treatment ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Uterine Cancer ◽  
Expression Level ◽  
Control Group ◽  
Gynecologic Cancers ◽  
Expression Levels

Abstract The most common gynecologic cancers detected in women in Turkey are uterine cancer, ovarian cancer, and cervical cancer. These data reported that a mean of 3800 individuals were diagnosed with uterine cancer, 2790 were diagnosed with ovarian cancer, and 1950 were diagnosed with cervical cancer, and 400 individuals were diagnosed with other gynecologic cancers each year in Turkey. A mean of 14.270 individuals were detected to have been diagnosed with gynecologic cancers each year in the United States of America(USA). Ovarian cancer treatment is generally composed of chemotherapy, and surgery. In general, chemotherapy is administered after surgery. The identification of the molecular pathogenesis of ovarian cancer, and discovery of new moleculer biomarkers which facilitate the ovarian cancer treatment are required for an effective ovarian cancer treatment in clinics. miRNAs are reported to be the possible biologic indicators for various cancer types. We aimed to investigate 2 miRNAs which were suggested to have effect in ovarian cancer in our (previous)monozygotic twin study from miR-1260 microRNA family whose association with ovarian cancer yet has not been reported in the literature. We investigated the expression levels of miR-1260a, and miR-1260b miRNAs, in the peripheral blood lymphocytes of 150 familial and sporadic ovarian cancer patients, and of 100 healthy individuals of the control group who were matched for age, sex, and ethnicity with the patient group, and investigated their possible property of being a biologic indicator for ovarian cancer. The expression results of ovarian cancer patients were evaluated by comparison of the results of the control group in the study. The expression levels of miR-1260a, and miR-1260b in ovarian cancer patients were found highly increased compared with the levels in the control group. miR-1260a expression level in ovarian cancer patients was detected to have increased approximately 17 fold compared with the control group, and miR-1260b expression level in ovarian cancer patients was detected to have increased approximately 33 fold compared with the levels in the control group. The String Analyses showed that the miR-1260a was associated with the ribosomal protein family which was known to be effective in the translation stage of cell and that miR-1260b was associated with CHEK2 protein which was a member of the serine/threonine-protein kinase family. It should be investigated for larger cohorts in benign ovarian diseases and in different stages of patients receiving ovarian cancer treatment whether these two molecules are a noninvasive biomarker and therapeutic target to be used especially in the early diagnosis and prognosis of ovarian cancer in future.

scholarly journals High expression level of miR-1260 family in the peripheral blood of patients with ovarian carcinoma

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Arash Adamnejad Ghafour ◽  
Demet Akdeniz Odemis ◽  
Seref Bugra Tuncer ◽  
Busra Kurt ◽  
Mukaddes Avsar Saral ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cervical Cancer ◽  
Cancer Treatment ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Uterine Cancer ◽  
Expression Level ◽  
Control Group ◽  
Gynecologic Cancers ◽  
Expression Levels

AbstractThe most common gynecologic cancers detected in women in Turkey are uterine cancer, ovarian cancer, and cervical cancer. These data reported that a mean of 3800 individuals were diagnosed with uterine cancer, 2790 were diagnosed with ovarian cancer, and 1950 were diagnosed with cervical cancer, and 400 individuals were diagnosed with other gynecologic cancers each year in Turkey. A mean of 14.270 individuals were detected to have been diagnosed with gynecologic cancers each year in the United States of America (USA). Ovarian cancer treatment is generally composed of chemotherapy, and surgery. In general, chemotherapy is administered after surgery. The identification of the molecular pathogenesis of ovarian cancer, and discovery of new moleculer biomarkers which facilitate the ovarian cancer treatment are required for an effective ovarian cancer treatment in clinics. miRNAs are reported to be the possible biologic indicators for various cancer types. We aimed to investigate 2 miRNAs which were suggested to have effect in ovarian cancer in our (previous) monozygotic twin study from miR-1260 microRNA family whose association with ovarian cancer yet has not been reported in the literature. We investigated the expression levels of miR-1260a, and miR-1260b miRNAs, in the peripheral blood lymphocytes of 150 familial and sporadic ovarian cancer patients, and of 100 healthy individuals of the control group who were matched for age, sex, and ethnicity with the patient group, and investigated their possible property of being a biologic indicator for ovarian cancer. The expression results of ovarian cancer patients were evaluated by comparison of the results of the control group in the study. The expression levels of miR-1260a, and miR-1260b in ovarian cancer patients were found highly increased compared with the levels in the control group. miR-1260a expression level in ovarian cancer patients was detected to have increased approximately 17 fold compared with the control group, and miR-1260b expression level in ovarian cancer patients was detected to have increased approximately 33 fold compared with the levels in the control group. The String Analyses showed that the miR-1260a was associated with the ribosomal protein family which was known to be effective in the translation stage of cell and that miR-1260b was associated with CHEK2 protein which was a member of the serine/threonine-protein kinase family. It should be investigated for larger cohorts in benign ovarian diseases and in different stages of patients receiving ovarian cancer treatment whether these two molecules are a noninvasive biomarker and therapeutic target to be used especially in the early diagnosis and prognosis of ovarian cancer in future.

Biologic meshes in cancer patients: A double-edged sword—Differences in production of IL6 and IL12 caused by acellular dermal matrices in human immune cells.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3064-3064
Author(s):  
Maria Margarete Guenthner-Biller ◽  
Sabine Enders ◽  
Julia Knabl ◽  
Verena Engelstaedter ◽  
Peter Duewell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Cancer Patients ◽  
Immune Cells ◽  
Statistical Difference ◽  
Wilcoxon Test ◽  
Dermal Matrices ◽  
Acellular Dermal

3064 Background: Acellular dermal matrices (ADM) have been used in different fields of surgery for almost 20 years. In 2005 Breuing et al first described its use in breast cancer patients. It is assumed that it is safe to use in an oncologic setting, but data from controlled studies are still missing. Because of its lack of cells ADM are considered not to cause an immune reaction. With increasing knowledge about the importance of immunology in breast cancer more information about ADM on different immune cell populations is needed. IL6 and IL12 are two central cytokines and key regulators of immune supression and activation. Methods: Strattice (ST; LifeCell) CollaMend (CM; Bard Davol), Biodesign (BD; Cook Biotec) as well as TiLoop a synthetic mesh (TL; pfm medical) were used in this study. We isolated myeloid dendritic cells (MDC), untouched plasmacytoid dendritic cells (PDC), naïve B-cells and CD8+ T-cells using the MACS System and co-cultered them with the biologic meshes or TL. For positive controls, we used CpG ODN 2216 3 µg/ml and LPS in a concentration of 100 ng/ml. Cytokine concentration of IL12p70 and IL6 were determined after seven days by using sandwich Elisa sets. Statistical significance was determined by the nonparametric Friedman-Test. The single hypothesis was calculated with a paired Wilcoxon Test. Results: There was a highly significant difference between the different ADM and TL in the immunologic response. The statistical difference for IL 6 was p= 0.0006131 for B cells and p= 0.00418 for T cells between TL and ADM. ST also caused significantly more IL6 than CM and BD. We found similar differences in IL 12 with p= 0.00194 for B cells and p= 0.003636 in T cells in regard to the difference between TL and ADM. For IL 12 there was no statistical difference between the ADM. We didn´t see any significant differences in the cytokine profile between the various ADM/TL in the MDC and PDC subpopulations. Conclusions: Despite the assumed lack of immune answer to ADM, immune cells reacted in our study with significantly different cytokine profiles. These findings can have implications regarding the activation or suppression of effector cells in a cancer patient.

T Cell Responses in Patients Vaccinated with Telomerase (hTERT)-mRNA Transfected Dendritic Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 373-373
Author(s):  
Else Marit Inderberg Suso ◽  
Anne-Marie Rasmussen ◽  
Steinar Aamdal ◽  
Svein Dueland ◽  
Gustav Gaudernack ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Cancer Patients ◽  
Cd8 T Cells ◽  
Stable Disease ◽  
T Cell Responses ◽  
Htert Mrna ◽  
Cell Responses

Abstract Abstract 373 Two cancer patients were vaccinated with dendritic cells (DC) loaded with telomerase (hTERT) mRNA to investigate the safety, tolerability and immunological response to vaccination prior to the start of a new phase I/II clinical trial. Following written informed consent one primary lung adenocarcinoma with metastasis and one patient with a relapsed pancreatic ductal type of adenocarcinoma, were treated with autologus monocyte-derived DC transfected with mRNA encoding hTERT. The patients first received four weekly injections administered intradermally followed by monthly booster injections. Peripheral blood mononuclear cells (PBMC) at each vaccination time point were tested in vitro with transfected DC and a panel of 24 overlapping hTERT peptides. In addition, hTERT-specific CD8+ T cells were monitored by pentamer staining. The treatment was well tolerated with minor side effects. Immune responses against telomerase-transfected DC and some of the overlapping hTERT peptides were detected in both patients. We also detected hTERT-specific CD8+ T cells in both patients by pentamer staining in post-vaccination samples. The lung cancer patients obtained a stable disease that lasted 18 months while the patient with pancreas cancer who started the DC vaccination in July 2007 following palliative chemotherapy, still is in stable disease by continuously boost vaccination. T-cell responses against telomerase epitopes have also been identified in both non-vaccinated cancer patients and cancer patients previously vaccinated with telomerase peptide. Since patients with these findings often show extraordinary clinical courses of their disease we hypothesize that it exists a high degree of immunogenicity and HLA promiscuity for some telomerase epitopes. In this study we have shown that vaccination with hTERT-mRNA transfected DC is safe and able to induce robust immune responses to several telomerase T-cell epitopes both in CD4+ and CD8+ T cells. This opens up the possibility for a broad clinical application of mRNA hTERT DC vaccines. Furthermore, responding T cells identified in these patients are strong candidates for T-cell receptor cloning and the receptors identified can thereafter be transferred into T cells creating the next generation of immuno-gene therapy with retargeted T cells. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Enhanced Stimulation of Anti-Ovarian Cancer CD8+ T Cells by Dendritic Cells Loaded with Nanoparticle Encapsulated Tumor Antigen

2011 ◽  
Vol 65 (6) ◽  
pp. 597-609 ◽  
Author(s):  
Douglas J. Hanlon ◽  
Paulomi B. Aldo ◽  
Lesley Devine ◽  
Ayesha B. Alvero ◽  
Anna K. Engberg ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Tumor Antigen ◽  
Stimulation Of

scholarly journals Five Genes as Diagnostic Markers of Ischemic Stroke and Their Correlation with Immune Infiltration

2021 ◽  
Author(s):  
Meng Wang ◽  
Ruijie Zhang ◽  
Qiongfeng Guan ◽  
Yindan Yao ◽  
Liyuan Han
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Ischemic Stroke ◽  
Immune Cells ◽  
Immune Cell ◽  
Diagnostic Markers ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Γδt Cells ◽  
Negatively Associated

Abstract Background: This study aimed to identify potential diagnostic markers of ischemic stroke (IS) and discuss the function of immune cell infiltration during the pathological process. Methods: We used IS datasets from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified, and functional correlation analysis was performed. We then screened and verified the diagnostic markers of IS. We evaluated the infiltration of immune cells in infarcts using CIBERSORT and analyzed the correlation between diagnostic markers and infiltrating immune cells. Results: A total of 366 DEGs were screened in this study. Genes encoding CTSG, F13A1, PABPC1, ECHDC2, BIRC2 and infiltrating monocytes, M0 macrophages, activated dendritic cells, and neutrophils (area under the curve [AUC] = 0.945) were identified as diagnostic markers of IS. Immune cell infiltration analysis suggested that memory B cells, regulatory T cells, M0 macrophages, CD8 + T cells, γδT cells, activated natural killer cells, monocytes, activated mast cells, and neutrophils were involved in the IS process. Analysis of correlations between expressed genes and infiltrating immune cells found that CTSG was positively associated with M0 macrophages, F13A1 was positively associated with monocytes, PABPC1 was positively associated with activated dendritic cells, eosinophils were negatively associated with neutrophils, ECHDC2 was negatively associated with monocytes, and BIRC2 was positively associated with eosinophils. Conclusion: five genes and four types of immune cells were identified as diagnostic markers of IS, and immune cell infiltration may play an important role in the progression of IS.

scholarly journals Identification of the Key Serum Biomarkers to Diagnose and Predict Metastasis of Osteosarcoma Based on the Analysis of Immune Cell Infiltration Characteristics

2021 ◽  
Author(s):  
Zhihao Chen ◽  
Liubing Li ◽  
Ziyuan Li ◽  
Xi Wang ◽  
Mingxiao Han ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Serum Biomarkers ◽  
Differentially Expressed ◽  
Cell Infiltration ◽  
Diagnostic Model ◽  
Immune Cell Infiltration ◽  
Differentially Expressed Mirnas

Abstract Background: The potential functions of circular RNAs (circRNAs) and micro RNAs (miRNAs) in osteosarcoma (OS) have not been fully elucidated. Especially, the behavior and mechanism of immune responses in OS development and progression have not been fully demonstrated. It was reported that circRNAs and miRNAs can serve as biomarkers for the diagnosis, prognosis, and therapy of many cancers. This study aimed to identify novel key serum biomarkers to diagnose and predict metastasis of OS based on the analysis of immune cell infiltration characteristics.Methods: The differentially-expressed circRNAs (DEcircRNAs), differentially-expressed miRNAs (DEmiRNAs),and differentially-expressed mRNAs (DEmRNAs) of human OS were investigated based on the microarray data downloaded from Gene Expression Omnibus (GEO) datasets. Then, we analyzed immune characteristics pattern of tumor-infiltrating immune cells in OS. On this basis, we identified statistically-significant transcription factors and performed pathway enrichment analysis. Subsequently, we constructed protein-protein interaction (PPI) and competitive endogenous RNA (ceRNA) networks. Moreover, the biological characteristic of targets in ceRNA networks was proposed. Finally, the expression and diagnostic capability of these potential biomarkers from ceRNA network were confirmed by RT-qPCR in patients’ serum.Results: Seven differentially-expressed circRNAs (DEcircRNAs), 166 differentially-expressed miRNAs (DEmiRNAs) and 175 differentially-expressed mRNAs (DEmRNAs) were identified in total. The highest level of infiltration in OS patients were M0 macrophages, M2 macrophages and CD8+ T cells. Further, M0 macrophages and CD8+ T cells were showed the largest negative correlation coefficients. These significant immune characteristics pattern of tumor-infiltrating immune cells were revealed by the principal component analysis in OS. Moreover, we found 185 statistically-significant transcription factors in which the main significant molecules show the potential in immunotherapy of OS. Hsa-circ-0010220, hsa-miR-326, hsa-miR-338-3p, and FAM98A from ceRNA networks associated with immune cell infiltration were confirmed as the potential novel biomarkers for OS diagnosis, of which FAM98A could distinguish and predict metastasis. Most importantly, a novel diagnostic model consisting of the four promising biomarkers (hsa-circ-0010220, hsa-miR-326, hsa-miR-338-3p, and FAM98A) was highlighted with 0.928 AUC value.Conclusions: In summary, the potenial serum biomarkers to diagnose and predict metastasis of OS based on the analysis of immune cell infiltration characteristics were found, and a novel diagnostic model consisting of four promising serum biomarkers was proposed firstly. These results provided a new perspective for the immunotherapy of OS.

Blood Dendritic Cells Generated With Flt3 Ligand and CD40 Ligand Prime CD8+ T Cells Efficiently in Cancer Patients

2006 ◽  
Vol 29 (5) ◽  
pp. 499-511 ◽  
Author(s):  
Ian D. Davis ◽  
Qiyuan Chen ◽  
Leone Morris ◽  
Juliet Quirk ◽  
Maureen Stanley ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cancer Patients ◽  
Cd8 T Cells ◽  
Cd40 Ligand ◽  
Flt3 Ligand

scholarly journals Quality of Care and Outcomes of Patients With Gynecologic Malignancies Treated at Safety-Net Hospitals

2019 ◽  
Vol 3 (3) ◽  
Author(s):  
Charlotte R Gamble ◽  
Yongmei Huang ◽  
Ana I Tergas ◽  
Fady Khoury-Collado ◽  
June Y Hou ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cervical Cancer ◽  
Quality Of Care ◽  
Low Income ◽  
Uterine Cancer ◽  
Gynecologic Oncology ◽  
Safety Net ◽  
Readmission Rates ◽  
Gynecologic Cancers

Abstract Background Although safety-net hospitals (SNH) provide a valuable role serving vulnerable patients, the quality of gynecologic oncology care at these hospitals remains inadequately documented. We examined the quality of care at SNH for women with gynecologic cancers. Methods We used the National Cancer Database to identify hospitals that treated patients with uterine, ovarian, or cervical cancer from 2004 to 2015. Hospitals with the greatest proportion of uninsured patients or Medicaid beneficiaries were defined as SNH. Quality metrics were derived from evidence-based recommendations. Thirty-day mortality, readmission rates, and 5-year survival were calculated. Multivariable models were developed to determine the association between treatment at SNH and outcomes. Results Overall, 594 750 patients diagnosed with gynecologic cancer were treated at 1340 hospitals. Compared with non-SNH, patients at SNH were younger, more frequently racial minorities, low income, and had more aggressive histologies and advanced-stage tumors. SNH had lower rates of minimally invasive surgery for uterine cancer (62.3% vs 75.9%, P < .0001), debulking for ovarian cancer (83.6% vs 86.9%, P < .05), and lymph node assessment for all three cancer types (P < .05). Rates of chemotherapy for uterine and ovarian cancer was greater whereas concurrent chemoradiation for cervical cancer was lower (P < .05 for all). Thirty-day mortality and readmission rates were equivalent. Mortality was moderately worse for patients with stage IV ovarian cancer and stage II–III cervical cancer (P < .05) but were otherwise equivalent. Conclusions After adjusting for patient and tumor characteristics, women with gynecologic cancers treated at SNH receive lower-quality surgical care and equivalent medical care and a subset of these patients has modest decreases in survival.

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