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 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.

Membrane-Bound Fas (Apo-1/CD95) Ligand on Leukemic Cells: A Mechanism of Tumor Immune Escape in Leukemia Patients

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 3135-3140 ◽  
Author(s):  
Agnès Buzyn ◽  
Frederic Petit ◽  
Marina Ostankovitch ◽  
Suzanne Figueiredo ◽  
Bruno Varet ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Escape ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Cellular Immunotherapy ◽  
Activated T Cells ◽  
Tumor Immune Escape ◽  
Target Cell Line ◽  
Set Up ◽  
Almost All

Abstract There is evidence from bone marrow transplantation that T cells may be involved in the immunologic control of leukemia. But many patients relapse despite a potent graft-versus-leukemia effect mediated by allogeneic T cells. The expression of the FasL protein has been suggested as a mechanism of tumor immune escape. We, therefore, evaluated the capacity of leukemic cells from patients with acute or chronic myelogenous leukemia to escape the allogeneic or autologous immune response by bearing the FasL molecule. Although almost all leukemic cells express the 37-kD form of FasL, only 54% of acute myeloblastic leukemia and 27% of chronic myeloid leukemia (CML) cells bore a FasL with killing properties, as assessed by the ability of leukemic cells to cause the apoptosis of a Fas-sensitive target cell line or autologous activated T cells in 3 tested leukemic cases. Experiments with a recombinant Fas-Fc molecule confirmed the role of Fas/FasL in leukemic-mediated cell death. Only CML leukemic cells from certain individuals contained the 26-kD truncated form of FasL. Thus, myeloid leukemic cells from some, but not all patients can set up a mechanism of immune escape involving the Fas/FasL pathway. This leukemic escape may have implications for patients eligible for adoptive cellular 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 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 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.

Membrane-Bound Fas (Apo-1/CD95) Ligand on Leukemic Cells: A Mechanism of Tumor Immune Escape in Leukemia Patients

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 3135-3140
Author(s):  
Agnès Buzyn ◽  
Frederic Petit ◽  
Marina Ostankovitch ◽  
Suzanne Figueiredo ◽  
Bruno Varet ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Escape ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Cellular Immunotherapy ◽  
Activated T Cells ◽  
Tumor Immune Escape ◽  
Target Cell Line ◽  
Set Up ◽  
Almost All

There is evidence from bone marrow transplantation that T cells may be involved in the immunologic control of leukemia. But many patients relapse despite a potent graft-versus-leukemia effect mediated by allogeneic T cells. The expression of the FasL protein has been suggested as a mechanism of tumor immune escape. We, therefore, evaluated the capacity of leukemic cells from patients with acute or chronic myelogenous leukemia to escape the allogeneic or autologous immune response by bearing the FasL molecule. Although almost all leukemic cells express the 37-kD form of FasL, only 54% of acute myeloblastic leukemia and 27% of chronic myeloid leukemia (CML) cells bore a FasL with killing properties, as assessed by the ability of leukemic cells to cause the apoptosis of a Fas-sensitive target cell line or autologous activated T cells in 3 tested leukemic cases. Experiments with a recombinant Fas-Fc molecule confirmed the role of Fas/FasL in leukemic-mediated cell death. Only CML leukemic cells from certain individuals contained the 26-kD truncated form of FasL. Thus, myeloid leukemic cells from some, but not all patients can set up a mechanism of immune escape involving the Fas/FasL pathway. This leukemic escape may have implications for patients eligible for adoptive cellular immunotherapy.

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.

scholarly journals Mathematical Modelling of the Inhibitory Role of Regulatory T Cells in Tumor Immune Response

Complexity ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-21
Author(s):  
Zhongtao Yang ◽  
Cuihong Yang ◽  
Yueping Dong ◽  
Yasuhiro Takeuchi
Keyword(s):  
T Cells ◽  
Immune System ◽  
Regulatory T Cells ◽  
Immune Cells ◽  
Immune Escape ◽  
Critical Value ◽  
Inhibitory Effect ◽  
Tumor Escape ◽  
Tumor Immune Escape ◽  
Stimulation Rate

The immune system against tumors acts through a complex dynamical process showing a dual role. On the one hand, the immune system can activate some immune cells to kill tumor cells (TCs), such as cytotoxic T lymphocytes (CTLs) and natural killer cells (NKs), but on the other hand, more evidence shows that some immune cells can help tumor escape, such as regulatory T cells (Tregs). In this paper, we propose a tumor immune interaction model based on Tregs-mediated tumor immune escape mechanism. When helper T cells’ (HTCs) stimulation rate by the presence of identified tumor antigens is below critical value, the coexistence (tumor and immune) equilibrium is always stable in its existence region. When HTCs stimulation rate is higher than the critical value, the inhibition rate of effector cells (ECs) by Tregs can destabilize the coexistence equilibrium and cause Hopf bifurcations and produce a limit cycle. This model shows that Tregs might play a crucial role in triggering the tumor immune escape. Furthermore, we introduce the adoptive cellular immunotherapy (ACI) and monoclonal antibody immunotherapy (MAI) as the treatment to boost the immune system to fight against tumors. The numerical results show that ACI can control TCs more, while MAI can delay the inhibitory effect of Tregs on ECs. The result also shows that the combination of both immunotherapies can control TCs and reduce the inhibitory effect of Tregs better than a single immunotherapy can control.

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