scholarly journals Natural Compounds with Potential to Modulate Cancer Therapies and Self-Reactive Immune Cells

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 673 ◽  
Author(s):  
Rhiane Moody ◽  
Kirsty Wilson ◽  
Anthony Jaworowski ◽  
Magdalena Plebanski
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Immune Cells ◽  
Epigallocatechin Gallate ◽  
Cancer Recurrence ◽  
Cancer Therapies ◽  
Dna Mutations ◽  
Autoimmune Pathology ◽  
Therapy Option ◽  
New Treatments

Cancer-related deaths are approaching 10 million each year. Survival statistics for some cancers, such as ovarian cancer, have remained unchanged for decades, with women diagnosed at stage III or IV having over 80% chance of a lethal cancer recurrence after standard first-line treatment (reductive surgery and chemotherapy). New treatments and adjunct therapies are needed. In ovarian cancer, as in other cancers, the immune response, particularly cytotoxic (CD8+) T cells are correlated with a decreased risk of recurrence. As well as completely new antigen targets resulting from DNA mutations (neo-antigens), these T cells recognize cancer-associated overexpressed, re-expressed or modified self-proteins. However, there is concern that activation of self-reactive responses may also promote off-target pathology. This review considers the complex interplay between cancer-reactive and self-reactive immune cells and discusses the potential uses for various leading immunomodulatory compounds, derived from plant-based sources, as a cancer therapy option or to modulate potential autoimmune pathology. Along with reviewing well-studied compounds such as curcumin (from turmeric), epigallocatechin gallate (EGCG, from green tea) and resveratrol (from grapes and certain berries), it is proposed that compounds from novel sources, for example, native Australian plants, will provide a useful source for the fine modulation of cancer immunity in patients.

scholarly journals Regulatory T Cells in Human Ovarian Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Dong-Jun Peng ◽  
Rebecca Liu ◽  
Weiping Zou
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Immune Suppression ◽  
Immune Cells ◽  
Clinical Settings ◽  
Human Ovarian Cancer ◽  
Cancer Microenvironment ◽  
Cellular Mechanisms ◽  
And Function ◽  
Antigen Presenting

Multiple layers of suppressive components including regulatory T (TReg) cells, suppressive antigen-presenting cells, and inhibitory cytokines form suppressive networks in the ovarian cancer microenvironment. It has been demonstrated that as a major suppressive element, TRegcells infiltrate tumor, interact with several types of immune cells, and mediate immune suppression through different molecular and cellular mechanisms. In this paper, we focus on human ovarian cancer and will discuss the nature of TRegcells including their subsets, trafficking, expansion, and function. We will briefly review the development of manipulation of TRegcells in preclinical and clinical settings.

Dynamics of T-cell infiltration during the course of ovarian cancer: The gradual shift from a Th17 effector cell response to a predominant infiltration by regulatory T cells.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22129-e22129
Author(s):  
Simona Partlova ◽  
Anna Fialova ◽  
Ludek Sojka ◽  
Lukas Rob ◽  
Jirina Bartunkova ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Culture ◽  
Flow Cytometry ◽  
T Cells ◽  
Regulatory T Cells ◽  
Tumor Cell ◽  
Immune Cells ◽  
Tumor Tissue ◽  
Tumor Cell Culture ◽  
Culture Supernatants

e22129 Background: Ovarian cancer is diagnosed in more than 190,000 new patients every year and is known to have the highest mortality rate among gynaecologic cancers. The type of immune cells that are present within the tumor microenvironment can play a crucial role in the survival of patients. However, little is known about the dynamics of the tumor-infiltrating immune cells during disease progression. Methods: We studied the immune cells infiltrating the tumor tissue of ovarian cancer patients at different stages of disease. We analysed the patterns of T lymphocytes in fresh tumor tissue as well as blood samples of 44 newly diagnosed ovarian cancer patients by flow cytometry. To evaluate whether regulatory T cells (Tregs) develop in situ or migrate to tumor tissue, we measured a concentration of chemokine CCL22 in tumor cell culture supernatants. We also determined the expression of CCR4 on circulating as well as tumor-infiltrating Tregs by flow cytometry. Results: The early stages of development of ovarian carcinomas were characterized by a strong Th17 immune response, whereas in stage II patients, recruitment of high numbers of Th1 cells was observed. In disseminated tumors (stage III-IV), we detected a dominant population of Helios+ activated regulatory T cells along with high numbers of macrophages and immature myeloid dendritic cells. Tumor-infiltrating Tregs had markedly lower expression of CCR4 than circulating Tregs, and the numbers of tumor-infiltrating Tregs significantly correlated with the levels of CCL22 in ovarian tumor cell culture supernatants, suggesting their recruitment via a CCR4/CCL22 interaction. CCL22 was mainly produced by tumor cells, macrophages and mDCs in the primary ovarian tumors, and its expression markedly increased in response to IFNgamma. Conclusions: Taken together, the specific recruitment of Tregs, probably triggered by inflammatory stimuli, leads to a significant immune suppression in the advanced stages of ovarian cancer.

scholarly journals CXCL13 Correlates with Prognosis, Immune Infiltration, and T Cell Exhaustion in Ovarian Cancer

2021 ◽  
Author(s):  
Hailing Duan ◽  
Ying Lv ◽  
Pan Liao ◽  
Yiming Wang ◽  
Zhifang Zheng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Cell Adhesion ◽  
T Cell ◽  
Immune Cells ◽  
Gene Marker ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Immune Infiltration ◽  
Prognosis Prediction

Abstract Background: CXCL13 is an important chemotactic factor closely related to the biology of cancer cells. The presence work focused on exploring the significance of CXCL13 in prognosis prediction and analyzing the associations of CXCL13 with T cell function and immune infiltration in various cancers, especially ovarian cancer (OV).Purpose: CXCL13 is associated with prognosis, immune infiltration, and T cell failure of ovarian cancer.Methods: The Oncomine, GEPIA2 and HPA databases were utilized for analyzing CXCL13 levels within diverse cancers. The significance of CXCL13 in prognosis prediction was explored through Kaplan-Meier Plotter, TCGAportal, and GEPIA2. Meanwhile, the associations of CXCL13 with clinical stage, gene marker sets, and immune infiltration were examined through TISIDB, GEPIA2, and TIMER databases. Besides, CXCL13 was screened to analyze the biological processes (BPs) and KEGGs enriched by co-expression genes. The miRWalk database was employed for analyzing the gene-miRNA interaction network of CXCL13 within OV.Results: CXCL13 expression decreased in many cancers, which predicted the dismal survival of OV. CXCL13 upregulation was in direct proportion to the increased immune infiltration degrees of many functional T cells (like exhausted T cells) and immune cells. Additionally, some critical genes of exhausted T cells, such as TIM-3, PD-1, LAG3, TIGIT, GZMB, and CXCL13, were closely associated with CXCL13. Moreover, CXCL13 was related to immune response regulatory signaling pathway, leukocyte cell-cell adhesion, cell adhesion molecules (CAMs), and hematopoietic cell lineage. Conclusion: CXCL13 can serve as a biomarker to predict cancer prognosis, particularly OV. CXCL13 upregulation remarkably elevates the immune infiltration degrees of numerous immune cells, like mast cells, CD8+ T cells, natural killer (NK) cells, and dendritic cells (DCs). Furthermore, CXCL13 is suggested to be closely related to exhausted T cells, which may be used as a candidate regulating factor for T cell exhaustion within OV. Detecting CXCL13 levels contributes to prognosis prediction and CXCL13 regulation within exhausted T cells, which provides a new approach to maximizing the anti-OV efficacy of immunotherapy.

scholarly journals Association of Immunosuppression with DR6 Expression during the Development and Progression of Spontaneous Ovarian Cancer in Laying Hen Model

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Sa’Rah McNeal ◽  
Pincas Bitterman ◽  
Janice M. Bahr ◽  
Seby L. Edassery ◽  
Jacques S. Abramowicz ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Tumor Progression ◽  
Peritoneal Cavity ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Laying Hen ◽  
Immune Functions ◽  
Late Stages

Ovarian cancer (OVCA) mainly disseminates in the peritoneal cavity. Immune functions are important to prevent OVCA progression and recurrence. The mechanism of immunosuppression, a hallmark of tumor progression, is not well understood. The goal of this study was to determine the immune system’s responses and its suppression during OVCA development and progression in hens. Frequencies of CD8+ T cells and IgY-containing cells and expression of immunosuppressors including IRG1 and DR6 in OVCA at early and late stages in hens were examined. Frequencies of stromal but not the intratumoral CD+8 T cells and IgY-containing cells increased significantly (P<0.01) during OVCA development and progression. Tumor progression was associated with increased expression of IRG1 and DR6 and decreased infiltration of immune cells into the tumor. Frequency of stromal but not intratumoral immune cells increases during OVCA development and progression. Tumor-induced IRG1 and DR6 may prevent immune cells from invading the tumor.

Procancerous immune cells in primary tumor is associated with breast cancer recurrence.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13042-e13042
Author(s):  
Takashi Takeshita ◽  
Li Yan ◽  
Kazuaki Takabe
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Immune Cells ◽  
Clinical Characteristics ◽  
Immune Cell ◽  
Cancer Recurrence ◽  
Early Death ◽  
Late Recurrence ◽  
Gene Expression Signatures ◽  
Or Gene

e13042 Background: Breast cancer (BC) recurrence is largely determined by cancer factors as well as host factors. It has been implicated that infiltrating immune cells play critical roles in long term survival. We hypothesize that immune cell infiltration profile rather than clinical characteristics or gene expression signatures of the primary tumors associate with the timing of cancer recurrence. Methods: 308 primary BCs in TCGA with cancer recurrence data was divided into; recurrence < 2 years (Early, n = 103), 2-5 years (Late, n = 20), and no recurrence > 5 years (Control, n = 185). 1410 primary BCs in METABRIC with BC specific death data was divided into; death < 10 years (Early Death, n = 499), death > 10 years (Late Death, n = 123), and survived > 10 years (Survivors, n = 788). Results: We found that Early tumors demonstrated more aggressive clinical characteristics such as larger tumor, more lymph node metastases, higher pathological grades, higher Stages, and negative estrogen and progesterone receptors, compared with Control tumors. On the other hand, no clinical characteristics of Late tumors were significantly different from Control tumors, which implicate that clinical characteristics cannot distinguish late recurrence from Control. Gene set enrichment analyses revealed that there was no significant gene sets that enriched with Early nor Late recurrence compared with Control, which implicate that gene expression signatures cannot distinguish recurrent tumor from Control. Utilizing CIBERSORT algorithm, we found that M1 was low and M2 was high macrophages in Early compared from Control. Further, anti-cancer lymphocytes, memory CD4 T cells and gamma delta T cells, were significantly lower, and pro-cancerous regulatory T cells were significantly higher in Early and Late compared from Control. In agreement, cytolytic activity score that assess immune cell killing were significantly lower in Early and Late compared from Control. Interestingly, only elevation of regulatory T cells was similar in METABRIC cohort when Early Death and Late Death were compared with Survivors. Conclusions: We found that not clinical characteristics or gene expression signatures, but pro-cancerous immune cells in primary BC associate with cancer recurrence and breast specific death.

scholarly journals P03.01 Prevalence of CD112R+immune cells in normal lymphatic tissues, inflammation and the cancer microenvironment

2020 ◽  
Vol 8 (Suppl 2) ◽  
pp. A22.1-A22
Author(s):  
NC Blessin ◽  
T Mandelkow ◽  
E Bady ◽  
C Hube-Magg ◽  
R Simon ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Immune Cells ◽  
T Helper Cells ◽  
Checkpoint Inhibitors ◽  
Cytotoxic T Cells ◽  
Small Subset ◽  
Cancer Microenvironment ◽  
T Helper ◽  
Helper Cells

BackgroundCD112R is an inhibitory immune checkpoint receptor and a putative target for novel immune therapies, but little is known about its molecular epidemiology in healthy and diseased tissues.Materials and MethodsTo study the prevalence and expression level of CD112R+ immune cells, we analyzed more than 200 samples of normal lymphatic, inflamed and cancerous tissues in a microenvironment tissue microarray format (4 mm tissue spot diameter) and large sections using fluorescent multiplex immunohistochemistry.ResultsCD112R expression was detected at variable intensity levels in 47% of CD8+ cytotoxic lymphocytes, 49% of CD4+ T helper cells, 30% of FOXP3+ regulatory T helper cells and in 25% of CD56+ natural killer cells, but no expression was seen in CD11c+ dendritic cells and CD68+ macrophages. All analyzed compartments across normal and diseased tissues showed a small subset (CD8: 9±18%, CD4: 5±15%, FOXP3: 2±5%) of immune cells with supramaximal CD112R expression. The highest fraction of cells with supramaximal CD112R expression was found in the subset of CD8+ cytotoxic T cells in the Peyer’s patches of ileum (62%), the intergranuloma area of lymph node sarcoidosis (27%) and in ovarian cancer (37%). In cancerous tissues, the density and the fraction cytotoxic T cells with supramaximal CD112R expression was highly variable and ranged from 5% in bladder cancer to 3% in lung cancer and 36% in ovarian cancer. A high variability of the number of cells with supramaximal CD112R expression was also seen within every tumor entity.ConclusionsIn summary, our analysis shows that CD112R expression is abundant in various subsets of immune cells but identifies a small fraction of cells with exceedingly high CD112R levels. The widespread occurrence of CD112R+ cytotoxic T cells in the cancer microenvironment may suggest considerable opportunities for checkpoint inhibitors targeting CD112R.Disclosure InformationN.C. Blessin: None. T. Mandelkow: None. E. Bady: None. C. Hube-Magg: None. R. Simon: None. G. Sauter: None. C. Fraune: None. M. Lennartz: None. K. Möller: None. D. Höflmayer: None. S.A. Weidemann: None.

scholarly journals Comprehensive analysis of prognostic gene signatures based on immune infiltration of ovarian cancer

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Shibai Yan ◽  
Juntao Fang ◽  
Yongcai Chen ◽  
Yong Xie ◽  
Siyou Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Immune Cells ◽  
Malignant Tumors ◽  
Treatment Strategies ◽  
Risk Groups ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Consensus Clustering ◽  
Immune Infiltration

Abstract Background Ovarian cancer (OV) is one of the most common malignant tumors of gynecology oncology. The lack of effective early diagnosis methods and treatment strategies result in a low five-year survival rate. Also, immunotherapy plays an important auxiliary role in the treatment of advanced OV patient, so it is of great significance to find out effective immune-related tumor markers for the diagnosis and treatment of OV. Methods Based on the consensus clustering analysis of single-sample gene set enrichment analysis (ssGSEA) score transformed via The Cancer Genome Atlas (TCGA) mRNA profile, we obtained two groups with high and low levels of immune infiltration. Multiple machine learning methods were conducted to explore prognostic genes associated with immune infiltration. Simultaneously, the correlation between the expression of mark genes and immune cells components was explored. Results A prognostic classifier including 5 genes (CXCL11, S1PR4, TNFRSF17, FPR1 and DHRS95) was established and its robust efficacy for predicting overall survival was validated via 1129 OV samples. Some significant variations of copy number on gene loci were found between two risk groups and it showed that patients with fine chemosensitivity has lower risk score than patient with poor chemosensitivity (P = 0.013). The high and low-risk groups showed significantly different distribution (P < 0.001) of five immune cells (Monocytes, Macrophages M1, Macrophages M2, T cells CD4 menory and T cells CD8). Conclusion The present study identified five prognostic genes associated with immune infiltration of OV, which may provide some potential clinical implications for OV treatment.

scholarly journals Myeloid-derived suppressor cells at diagnosis may discriminate between benign and malignant ovarian tumors

2019 ◽  
Vol 29 (9) ◽  
pp. 1381-1388 ◽  
Author(s):  
An Coosemans ◽  
Thaïs Baert ◽  
Jolien Ceusters ◽  
Pieter Busschaert ◽  
Chiara Landolfo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Immune System ◽  
Natural Killer Cells ◽  
Regulatory T Cells ◽  
Natural Killer ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Killer Cells

BackgroundThe behavior of the immune system as a driver in the progression of ovarian cancer has barely been studied. Our knowledge is mainly limited to the intra-tumoral adaptive immune system. Because of the widespread metastases of ovarian cancer, an assessment of the circulating immune system seems more accurate.To demonstrate the presence of immune cells in blood samples of patients with ovarian neoplasms.MethodsIn this exploratory prospective cohort study, peripheral blood mononuclear cells were collected at diagnosis from 143 women, including 62 patients with benign cysts, 13 with borderline tumor, 41 with invasive ovarian cancer, and 27 age-matched healthy controls. Immune profile analyses, based on the presence of CD4 (cluster of differentiation), CD8, natural killer cells, myeloid-derived suppressor cells, and regulatory T cells, were performed by fluorescence activated cell sorting.ResultsIn a multivariable analysis, six immune cells (activated regulatory T cells, natural killer cells, myeloid-derived suppressor cells, monocytic myeloid-derived suppressor cells, exhausted monocytic myeloid-derived suppressor cells, and total myeloid cells) were selected as independent predictors of malignancy, with an optimism-corrected area under the receiver operating characteristic curve (AUC) of 0.858. In contrast, a profile based on CD8 and regulatory T cells, the current standard in ovarian cancer immunology, resulted in an AUC of 0.639.ConclusionsOur immune profile in blood suggests an involvement of innate immunosuppression driven by myeloid-derived suppressor cells in the development of ovarian cancer. This finding could contribute to clinical management of patients and in selection of immunotherapy.

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 Immune Modulatory Properties of Collagen in Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Anne Mette Askehøj Rømer ◽  
Marie-Louise Thorseth ◽  
Daniel Hargbøl Madsen
Keyword(s):  
T Cells ◽  
Cancer Immunotherapy ◽  
Cancer Progression ◽  
Immune Cells ◽  
Poor Prognosis ◽  
Current Knowledge ◽  
Cell Activity ◽  
Cancer Therapies ◽  
Cell Growth And Migration ◽  
Collagen Density

During tumor growth the extracellular matrix (ECM) undergoes dramatic remodeling. The normal ECM is degraded and substituted with a tumor-specific ECM, which is often of higher collagen density and increased stiffness. The structure and collagen density of the tumor-specific ECM has been associated with poor prognosis in several types of cancer. However, the reason for this association is still largely unknown. Collagen can promote cancer cell growth and migration, but recent studies have shown that collagens can also affect the function and phenotype of various types of tumor-infiltrating immune cells such as tumor-associated macrophages (TAMs) and T cells. This suggests that tumor-associated collagen could have important immune modulatory functions within the tumor microenvironment, affecting cancer progression as well as the efficacy of cancer immunotherapy. The effects of tumor-associated collagen on immune cells could help explain why a high collagen density in tumors is often correlated with a poor prognosis. Knowledge about immune modulatory functions of collagen could potentially identify targets for improving current cancer therapies or for development of new treatments. In this review, the current knowledge about the ability of collagen to influence T cell activity will be summarized. This includes direct interactions with T cells as well as induction of immune suppressive activity in other immune cells such as macrophages. Additionally, the potential effects of collagen on the efficacy of cancer immunotherapy will be discussed.

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