scholarly journals Recent advances in understanding immune phenotypes of thyroid carcinomas: prognostication and emerging therapies

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 227 ◽  
Author(s):  
Federica Liotti ◽  
Nella Prevete ◽  
Giancarlo Vecchio ◽  
Rosa Marina Melillo
Keyword(s):  
Clinical Trials ◽  
Thyroid Cancer ◽  
Immune Cells ◽  
Immune Escape ◽  
Immunosuppressive Activity ◽  
Tumor Immune Escape ◽  
System A ◽  
Emerging Therapies ◽  
Tumor Immunogenicity ◽  
Immune Phenotypes

Tumors modulate the host immune cells within their microenvironment to avoid recognition and elimination by our immune system, a phenotype called cancer immune escape. Different mechanisms responsible for cancer immune escape that result either in decreased tumor immunogenicity or in increased tumor immunosuppressive activity have been identified. Recently, various immunotherapeutic approaches have been developed with the aim to revert tumor immune escape. The aims of this review are to explore the immunological aspects of thyroid cancer and to assess whether these features can be exploited in the prognosis and treatment of advanced forms of this disease. Therefore, we will describe the immune landscape and phenotypes of thyroid cancer, summarize studies investigating the expression of immunomodulatory molecules, and finally describe the preclinical and clinical trials investigating the utility of immunotherapies in the management of thyroid cancer. The aim of this review is to explore the immunological aspects of thyroid cancer and to assess whether these features can be exploited in the prognosis and treatment of advanced forms of this disease. Therefore, we will describe the immune-landscape and phenotypes of thyroid cancer, we will summarize studies investigating the expression of immunomodulatory molecules, and we will finally describe the preclinical and clinical trials investigating the utility of immunotherapies in the management of thyroid cancer.

scholarly journals Unveiling the immune infiltrate modulation in cancer and response to immunotherapy by MIXTURE—an enhanced deconvolution method

2020 ◽  
Author(s):  
Elmer A Fernández ◽  
Yamil D Mahmoud ◽  
Florencia Veigas ◽  
Darío Rocha ◽  
Matías Miranda ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Cells ◽  
Immune Cell ◽  
Immune Escape ◽  
Intratumor Heterogeneity ◽  
Support Vector ◽  
Tumor Immune Escape ◽  
Immune Infiltrate ◽  
Tumor Biopsies

Abstract The accurate quantification of tumor-infiltrating immune cells turns crucial to uncover their role in tumor immune escape, to determine patient prognosis and to predict response to immune checkpoint blockade. Current state-of-the-art methods that quantify immune cells from tumor biopsies using gene expression data apply computational deconvolution methods that present multicollinearity and estimation errors resulting in the overestimation or underestimation of the diversity of infiltrating immune cells and their quantity. To overcome such limitations, we developed MIXTURE, a new ν-support vector regression-based noise constrained recursive feature selection algorithm based on validated immune cell molecular signatures. MIXTURE provides increased robustness to cell type identification and proportion estimation, outperforms the current methods, and is available to the wider scientific community. We applied MIXTURE to transcriptomic data from tumor biopsies and found relevant novel associations between the components of the immune infiltrate and molecular subtypes, tumor driver biomarkers, tumor mutational burden, microsatellite instability, intratumor heterogeneity, cytolytic score, programmed cell death ligand 1 expression, patients’ survival and response to anti-cytotoxic T-lymphocyte-associated antigen 4 and anti-programmed cell death protein 1 immunotherapy.

scholarly journals Research progress on the role of sialic acid-binding immunoglobulin-like lectin 9 in various diseases

2021 ◽  
Vol 5 (2.1) ◽  
pp. 51
Author(s):  
Ling Cao ◽  
Xiaoliang Yuan
Keyword(s):  
Sialic Acid ◽  
Autoimmune Diseases ◽  
Inflammatory Cytokines ◽  
Immune Cells ◽  
Immune Escape ◽  
Research Progress ◽  
Tumor Immune Escape ◽  
Sialic Acid Binding ◽  
Pro Inflammatory Cytokines

Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a receptor that expresses on the surface of immune cells. It plays an important role in the body’s immune response. Increased expression of Siglec-9 has been reported in infectious diseases, autoimmune diseases and cancer. Pathogenic microorganism and tumor cells can inhibit the recognition and killing of immune cells by upregulating their own specific sialic acid and binding with Siglec-9 on the surface of host immune cells, and suppress the release of pro-inflammatory cytokines and promote the release of anti-inflammatory cytokines, eventually leading to immunosuppression, tumor immune escape and the like. However, the immunosuppressive function of Siglec-9 may be advantageous for diseases such as neutrophil asthma and autoimmune diseases. Therefore, further research on the mechanism of action of Siglec-9 is of great significance.

scholarly journals Epithelial-Mesenchymal Plasticity in Organotropism Metastasis and Tumor Immune Escape

2019 ◽  
Vol 8 (5) ◽  
pp. 747 ◽  
Author(s):  
Xiang Nan ◽  
Jiang Wang ◽  
Haowen Nikola Liu ◽  
Stephen T.C. Wong ◽  
Hong Zhao
Keyword(s):  
Experimental Evidence ◽  
Immune Cells ◽  
Cellular Differentiation ◽  
Recent Progress ◽  
Immune Escape ◽  
Metastatic Niche ◽  
Tumor Immune Escape ◽  
Organ Specific ◽  
Almost All ◽  
Organotropic Metastasis

Most cancer deaths are due to metastasis, and almost all cancers have their preferential metastatic organs, known as “organotropism metastasis”. Epithelial-mesenchymal plasticity has been described as heterogeneous and dynamic cellular differentiation states, supported by emerging experimental evidence from both molecular and morphological levels. Many molecular factors regulating epithelial-mesenchymal plasticity have tissue-specific and non-redundant properties. Reciprocally, cellular epithelial-mesenchymal plasticity contributes to shaping organ-specific pre-metastatic niche (PMN) including distinct local immune landscapes, mainly through secreted bioactive molecular factors. Here, we summarize recent progress on the involvement of tumor epithelial-mesenchymal plasticity in driving organotropic metastasis and regulating the function of different immune cells in organ-specific metastasis.

scholarly journals Bioinformatics Analysis of GFAP as a Potential Key Regulator in Different Immune Phenotypes of Prostate Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Wencheng Yao ◽  
Xiang Li ◽  
Zhankui Jia ◽  
Chaohui Gu ◽  
Zhibo Jin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Immune Escape ◽  
Interaction Analysis ◽  
Cancer Genome ◽  
Tumor Immune Escape ◽  
Potential Biomarker ◽  
Immune Phenotypes ◽  
Patient Subgroups

Tumor immune escape plays an essential role in both cancer progression and immunotherapy responses. For prostate cancer (PC), however, the molecular mechanisms that drive its different immune phenotypes have yet to be fully elucidated. Patient gene expression data were analyzed from The Cancer Genome Atlas-prostate adenocarcinoma (TCGA-PRAD) and the International Cancer Genome Consortium (ICGC) databases. We used a Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) analysis and an unsupervised clustering analysis to identify patient subgroups with distinct immune phenotypes. These distinct phenotypes were then explored for associations for differentially expressed genes (DEGs) and both epigenetic and genetic landscapes. Finally, we used a protein-protein interaction analysis to identify key hub genes. We identified two patient subgroups with independent immune phenotypes associated with the expression of Programmed death-ligand 1 (PD-L1). Patient samples in Cluster 1 ( C 1 ) had higher scores for immune-cell subsets compared to Cluster 2 ( C 2 ), and C 2 samples had higher specific somatic mutations, MHC mutations, and genomic copy number variations compared to C 1 . We also found additional cluster phenotype differences for DNA methylation, microRNA (miRNA) expression, and long noncoding RNA (lncRNA) expression. Furthermore, we established a 4-gene model to distinguish between clusters by integrating analyses for DEGs, lncRNAs, miRNAs, and methylation. Notably, we found that glial fibrillary acidic protein (GFAP) might serve as a key hub gene within the genetic and epigenetic regulatory networks. These results improve our understanding of the molecular mechanisms underlying tumor immune phenotypes that are associated with tumor immune escape. In addition, GFAP may be a potential biomarker for both PC diagnosis and prognosis.

scholarly journals Regulation of Tumor Immunity by Tumor/Dendritic Cell Fusions

2010 ◽  
Vol 2010 ◽  
pp. 1-14 ◽  
Author(s):  
Shigeo Koido ◽  
Sadamu Homma ◽  
Eiichi Hara ◽  
Yoshihisa Namiki ◽  
Akitaka Takahara ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Immune Responses ◽  
Immune Escape ◽  
Cytotoxic T Cells ◽  
Tumor Burden ◽  
Tumor Immune Escape ◽  
Tumor Associated Antigens ◽  
Reduce Tumor Burden ◽  
Tumor Environment ◽  
Cell Fusions

The goal of cancer vaccines is to induce antitumor immunity that ultimately will reduce tumor burden in tumor environment. Several strategies involving dendritic cells- (DCs)- based vaccine incorporating different tumor-associated antigens to induce antitumor immune responses against tumors have been tested in clinical trials worldwide. Although DCs-based vaccine such as fusions of whole tumor cells and DCs has been proven to be clinically safe and is efficient to enhance antitumor immune responses for inducing effective immune response and for breaking T-cell tolerance to tumor-associated antigens (TAAs), only a limited success has occurred in clinical trials. This paper reviews tumor immune escape and current strategies employed in the field of tumor/DC fusions vaccine aimed at enhancing activation of TAAs-specific cytotoxic T cells in tumor microenvironment.

scholarly journals The Combination of Immune Checkpoint Blockade and Angiogenesis Inhibitors in the Treatment of Advanced Non-Small Cell Lung Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Sijia Ren ◽  
Xinxin Xiong ◽  
Hua You ◽  
Jianfei Shen ◽  
Penghui Zhou
Keyword(s):  
Lung Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Immune Cells ◽  
Immune Escape ◽  
Immune Checkpoint Blockade ◽  
Small Cell ◽  
Vascular Endothelial ◽  
Small Cell Lung ◽  
Tumor Immune Escape ◽  
Endothelial Growth Factor

Immune checkpoint blockade (ICB) has become a standard treatment for non-small cell lung cancer (NSCLC). However, most patients with NSCLC do not benefit from these treatments. Abnormal vasculature is a hallmark of solid tumors and is involved in tumor immune escape. These abnormalities stem from the increase in the expression of pro-angiogenic factors, which is involved in the regulation of the function and migration of immune cells. Anti-angiogenic agents can normalize blood vessels, and thus transforming the tumor microenvironment from immunosuppressive to immune-supportive by increasing the infiltration and activation of immune cells. Therefore, the combination of immunotherapy with anti-angiogenesis is a promising strategy for cancer treatment. Here, we outline the current understanding of the mechanisms of vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) signaling in tumor immune escape and progression, and summarize the preclinical studies and current clinical data of the combination of ICB and anti-angiogenic drugs in the treatment of advanced NSCLC.

scholarly journals Inhibition of iNKT Cells by the HLA-G-ILT2 Checkpoint and Poor Stimulation by HLA-G-Expressing Tolerogenic DC

2021 ◽  
Vol 11 ◽  
Author(s):  
Ching-Lien Wu ◽  
Julien Caumartin ◽  
Giada Amodio ◽  
François Anna ◽  
Maria Loustau ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cell Activation ◽  
Cell Function ◽  
Immune Cell ◽  
Immune Escape ◽  
Inkt Cell ◽  
Inkt Cells ◽  
Tumor Immune Escape ◽  
Checkpoint Molecule ◽  
Antigen Presenting

Invariant Natural Killer T (iNKT) cells are a small and distinct population of T cells crucial in immunomodulation. After activation by alpha-GalactosylCeramide (αGC), an exogenic glycolipid antigen, iNKT cells can rapidly release cytokines to enhance specific anti-tumor activity. Several human clinical trials on iNKT cell-based anti-cancer are ongoing, however results are not as striking as in murine models. Given that iNKT-based immunotherapies are dependent mainly on antigen-presenting cells (APC), a human tolerogenic molecule with no murine homolog, such as Human Leucocyte Antigen G (HLA-G), could contribute to this discrepancy. HLA-G is a well-known immune checkpoint molecule involved in fetal-maternal tolerance and in tumor immune escape. HLA-G exerts its immunomodulatory functions through the interaction with immune inhibitory receptors such as ILT2, differentially expressed on immune cell subsets. We hypothesized that HLA-G might inhibit iNKT function directly or by inducing tolerogenic APC leading to iNKT cell anergy, which could impact the results of current clinical trials. Using an ILT2-transduced murine iNKT cell line and human iNKT cells, we demonstrate that iNKT cells are sensitive to HLA-G, which inhibits their cytokine secretion. Furthermore, human HLA-G+ dendritic cells, called DC-10, failed at inducing iNKT cell activation compared to their autologous HLA-G‒ DCs counterparts. Our data show for the first time that the HLA-G/ILT2 ICP is involved in iNKT cell function modulation.

scholarly journals p50 suppresses cytotoxic T lymphocyte effector function to regulate tumor immune escape and response to immunotherapy

2020 ◽  
Vol 8 (2) ◽  
pp. e001365 ◽  
Author(s):  
Chunwan Lu ◽  
John D Klement ◽  
Alyssa D Smith ◽  
Dafeng Yang ◽  
Jennifer L Waller ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Tumor Cells ◽  
Immune Cells ◽  
Expression Profiling ◽  
Immune Escape ◽  
Human Colon ◽  
Tumor Immune Escape ◽  
Human Colorectal Carcinoma

BackgroundNF-κB is a key link between inflammation and cancer. Previous studies of NF-κB have largely focused on tumor cells, and the intrinsic function of NF-κB in T cells in tumor development and response to immunotherapy is largely unknown. We aimed at testing the hypothesis that NF-κB1 (p50) activation in T cells underlies human colon cancer immune escape and human cancer non-response to anti-PD-1 immunotherapy.MethodsWe screened NF-κB activation in human colon carcinoma and used mouse models to determine p50 function in tumor cells and immune cells. RNA-Seq was used to identify p50 target genes. p50 binding to target gene promoters were determined by electrophoresis mobility shift assay and chromatin immunoprecipitation. A p50 activation score was generated from gene expression profiling and used to link p50 activation to T-cell activation and function pre-nivolumab and post-nivolumab immunotherapy in human patients with cancer.Resultsp50 is the dominant form of NF-κB that is highly activated in immune cells in the human colorectal carcinoma microenvironment and neighboring non-neoplastic colon epithelial cells. Tumor cell intrinsic p50 signaling and T-cell intrinsic p50 signaling exert opposing functions in tumor growth control in vivo. Deleting Nfkb1 in tumor cells increased whereas in T cells decreased tumor growth in preclinical mouse models. Gene expression profiling identified Gzmb as a p50 target in T cells. p50 binds directly to a previously uncharacterized κB sequence at the Gzmb promoter in T cells, resulting in repression of Gzmb expression in tumor-infiltrating cytotoxic T lymphocytes (CTLs) to induce a dysfunctional CTL phenotype to promote tumor immune escape. p50 activation is inversely correlated with both GZMB expression and T-cell tumor infiltration in human colorectal carcinoma. Furthermore, nivolumab immunotherapy decreased p50 activation and increased GZMB expression in human patients with melanoma.ConclusionsInflammation activates p50 that binds to the Gzmb promoter to repress granzyme B expression in T cells, resulting in CTL dysfunction to confer tumor immune escape and decreased response to anti-PD-1 immunotherapy.

scholarly journals What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment

2021 ◽  
Vol 22 (22) ◽  
pp. 12330
Author(s):  
Andrea Palicelli ◽  
Stefania Croci ◽  
Alessandra Bisagni ◽  
Eleonora Zanetti ◽  
Dario De Biase ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Microenvironment ◽  
Literature Review ◽  
Signaling Pathways ◽  
Systematic Literature Review ◽  
Immune Cells ◽  
Intracellular Signaling ◽  
Immune Escape ◽  
Tumor Immune Escape ◽  
Intracellular Signaling Pathways

The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and cytokines/chemokines/soluble factors regulating various intracellular signaling pathways (ISP) in tumor cells. TME influences the survival/progression of prostate cancer (PC), enabling tumor cell immune-evasion also through the activation of the PD-1/PD-L1 axis. We have performed a systematic literature review according to the PRISMA guidelines, to investigate how the PD-1/PD-L1 pathway is influenced by TME and ISPs. Tumor immune-escape mechanisms include suppression/exhaustion of tumor infiltrating cytotoxic T lymphocytes, inhibition of tumor suppressive NK cells, increase in immune-suppressive immune cells (regulatory T, M2 macrophagic, myeloid-derived suppressor, dendritic, stromal, and adipocytic cells). IFN-γ (the most investigated factor), TGF-β, TNF-α, IL-6, IL-17, IL-15, IL-27, complement factor C5a, and other soluble molecules secreted by TME components (and sometimes increased in patients’ serum), as well as and hypoxia, influenced the regulation of PD-L1. Experimental studies using human and mouse PC cell lines (derived from either androgen-sensitive or androgen-resistant tumors) revealed that the intracellular ERK/MEK, Akt-mTOR, NF-kB, WNT and JAK/STAT pathways were involved in PD-L1 upregulation in PC. Blocking the PD-1/PD-L1 signaling by using immunotherapy drugs can prevent tumor immune-escape, increasing the anti-tumor activity of immune cells.

scholarly journals The Immune Privilege of Cancer Stem Cells: A Key to Understanding Tumor Immune Escape and Therapy Failure

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2361
Author(s):  
Claudia Galassi ◽  
Martina Musella ◽  
Nicoletta Manduca ◽  
Ester Maccafeo ◽  
Antonella Sistigu
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Immune Cells ◽  
Immune Escape ◽  
Immune Therapy ◽  
Adaptive Immune System ◽  
Therapy Resistance ◽  
Tumor Immune Escape ◽  
Adaptive Immune ◽  
Histocompatibility Complex

Cancer stem cells (CSCs) are broadly considered immature, multipotent, tumorigenic cells within the tumor mass, endowed with the ability to self-renew and escape immune control. All these features contribute to place CSCs at the pinnacle of tumor aggressiveness and (immune) therapy resistance. The immune privileged status of CSCs is induced and preserved by various mechanisms that directly affect them (e.g., the downregulation of the major histocompatibility complex class I) and indirectly are induced in the host immune cells (e.g., activation of immune suppressive cells). Therefore, deeper insights into the immuno-biology of CSCs are essential in our pursuit to find new therapeutic opportunities that eradicate cancer (stem) cells. Here, we review and discuss the ability of CSCs to evade the innate and adaptive immune system, as we offer a view of the immunotherapeutic strategies adopted to potentiate and address specific subsets of (engineered) immune cells against CSCs.

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