scholarly journals Immuno-genomic PanCancer Landscape Reveals Diverse Immune Escape Mechanisms and Immuno-Editing Histories

2018 ◽  
Author(s):  
Shinichi Mizuno ◽  
Rui Yamaguchi ◽  
Takanori Hasegawa ◽  
Shuto Hayashi ◽  
Masashi Fujita ◽  
...  
Keyword(s):  
Immune Escape ◽  
Cancer Hallmarks ◽  
Whole Genomes ◽  
Immune Therapies ◽  
History Of ◽  
Copy Number Changes ◽  
Immune Related Genes ◽  
Tumor Types ◽  
Immune Escape Mechanisms

AbstractImmune reactions in the tumor micro-environment are one of the cancer hallmarks and emerging immune therapies have been proven effective in many types of cancer. To investigate cancer genome-immune interactions and the role of immuno-editing or immune escape mechanisms in cancer development, we analyzed 2,834 whole genomes and RNA-seq datasets across 31 distinct tumor types from the PanCancer Analysis of Whole Genomes (PCAWG) project with respect to key immuno-genomic aspects. We show that selective copy number changes in immune-related genes could contribute to immune escape. Furthermore, we developed an index of the immuno-editing history of each tumor sample based on the information of mutations in exonic regions and pseudogenes. Our immuno-genomic analyses of pan-cancer analyses have the potential to identify a subset of tumors with immunogenicity and diverse background or intrinsic pathways associated with their immune status and immuno-editing history.

scholarly journals Immunogenomic pan-cancer landscape reveals immune escape mechanisms and immunoediting histories

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shinichi Mizuno ◽  
Rui Yamaguchi ◽  
Takanori Hasegawa ◽  
Shuto Hayashi ◽  
Masashi Fujita ◽  
...  
Keyword(s):  
Immune Escape ◽  
Diverse Backgrounds ◽  
Immune Therapies ◽  
History Of ◽  
Copy Number Changes ◽  
Immune Related Genes ◽  
Tumor Types ◽  
Immune Escape Mechanisms ◽  
Pan Cancer

AbstractImmune reactions in the tumor microenvironment are an important hallmark of cancer, and emerging immune therapies have been proven effective against several types of cancers. To investigate cancer genome-immune interactions and the role of immunoediting or immune escape mechanisms in cancer development, we analyzed 2834 whole genome and RNA sequencing datasets across 31 distinct tumor types with respect to key immunogenomic aspects and provided comprehensive immunogenomic profiles of pan-cancers. We found that selective copy number changes in immune-related genes may contribute to immune escape. Furthermore, we developed an index of the immunoediting history of each tumor sample based on the information of mutations in exonic regions and pseudogenes and evaluated the immunoediting history of each tumor. Our immuno-genomic analyses of pan-cancers have the potential to identify a subset of tumors with immunogenicity and diverse backgrounds or intrinsic pathways associated with their immune status and immunoediting history.

scholarly journals The role of tumor-derived exosomes in tumor immune escape: A concise review

2020 ◽  
Vol 7 (11) ◽  
pp. 4132-4137
Author(s):  
Nhat Chau Truong ◽  
Thao Nhi Huynh ◽  
Khuong Duy Pham ◽  
Phuc Van Pham
Keyword(s):  
Immune Modulation ◽  
Immune Escape ◽  
Suppressor Cells ◽  
Target Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Immune Escape ◽  
Concise Review ◽  
Viable Cells ◽  
Immune Escape Mechanisms

Exosomes are small vesicles secreted by viable cells into the microenvironment. These vesicles bring various compositions, including lipids, RNAs and proteins, which carry information from producer cells to target cells. Cancer cells also produce exosomes, termed as tumor-derived exosomes (TDEs), which play important roles in immune modulation, angiogenesis and metastasis of tumors. This review summarizes the roles of TDEs in tumor immune escape mechanisms. TDEs affect all kinds of tumor-associated immune cells, including natural killer (NK) cells, dendritic cells (DCs), T and B lymphocytes, and myeloid-derived suppressor cells (MDSCs). Generally, TDEs suppress the immune system to promote tumor immune escape, thereby significantly contributing to tumorigenesis and metastasis.

scholarly journals The Interplay of Reactive Oxygen Species, Hypoxia, Inflammation, and Sirtuins in Cancer Initiation and Progression

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Marco Tafani ◽  
Luigi Sansone ◽  
Federica Limana ◽  
Tania Arcangeli ◽  
Elena De Santis ◽  
...  
Keyword(s):  
Natural History ◽  
Gene Mutations ◽  
Suppressor Gene ◽  
Malignant Progression ◽  
Initial Growth ◽  
Cancer Hallmarks ◽  
Beneficial Effects ◽  
Cancer Initiation ◽  
History Of

The presence of ROS is a constant feature in living cells metabolizing O2. ROS concentration and compartmentation determine their physiological or pathological effects. ROS overproduction is a feature of cancer cells and plays several roles during the natural history of malignant tumor. ROS continuously contribute to each step of cancerogenesis, from theinitiationto themalignant progression, acting directly or indirectly. In this review, we will (a) underline the role of ROS in the pathway leading a normal cell to tumor transformation and progression, (b) define the multiple roles of ROS during the natural history of a tumor, (c) conciliate many conflicting data about harmful or beneficial effects of ROS, (d) rethink the importance of oncogene and tumor suppressor gene mutations in relation to the malignant progression, and (e) collocate all the cancer hallmarks in a mechanistic sequence which could represent a “physiological” response to the initial growth of a transformed stem/pluripotent cell, defining also the role of ROS in each hallmark. We will provide a simplified sketch about the relationships between ROS and cancer. The attention will be focused on the contribution of ROS to the signaling of HIF, NFκB, and Sirtuins as a leitmotif of cancer initiation and progression.

scholarly journals Mechanisms of EGFR Resistance in Glioblastoma

2020 ◽  
Vol 21 (22) ◽  
pp. 8471
Author(s):  
Peter C. Pan ◽  
Rajiv S. Magge
Keyword(s):  
Growth Factor Receptor ◽  
Extracellular Domain ◽  
Kinase Domain ◽  
Small Cell ◽  
Small Cell Lung ◽  
History Of ◽  
Epidermal Growth ◽  
Tumor Types ◽  
Primary Malignant Brain Tumor

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Despite numerous efforts to target epidermal growth factor receptor (EGFR), commonly dysregulated in GBM, approaches directed against EGFR have not achieved the same degree of success as seen in other tumor types, particularly as compared to non-small cell lung cancer (NSCLC). EGFR alterations in glioblastoma lie primarily in the extracellular domain, unlike the kinase domain alterations seen in NSCLC. Small molecule inhibitors are difficult to develop for the extracellular domain. Monoclonal antibodies can be developed to target the extracellular domain but must contend with the blood brain barrier (BBB). We review the role of EGFR in GBM, the history of trialed treatments, and the potential paths forward to target the pathway that may have greater success.

scholarly journals Murine Models of B-Cell Lymphomas: Promising Tools for Designing Cancer Therapies

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Sabrina Donnou ◽  
Claire Galand ◽  
Valérie Touitou ◽  
Catherine Sautès-Fridman ◽  
Zsuzsanna Fabry ◽  
...  
Keyword(s):  
B Cell ◽  
Immune Escape ◽  
Hematologic Malignancy ◽  
Cancer Therapies ◽  
Murine Models ◽  
B Cell Lymphomas ◽  
Cellular Mechanisms ◽  
New Therapies ◽  
Immune Escape Mechanisms

Human B-cell lymphomas, the fourth most common hematologic malignancy, are currently the subject of extensive research. The limited accessibility of biopsies, the heterogeneity among patients, and the subtypes of lymphomas have necessitated the development of animal models to decipher immune escape mechanisms and design new therapies. Here, we summarize the cell lines and murine models used to study lymphomagenesis, the lymphoma microenvironment, and the efficacy of new therapies. These data allow us to understand the role of the immune system in the fight against tumors. Exploring the advantages and limitations of immunocompetent versus immunodeficient models improves our understanding of the molecular and cellular mechanisms of tumor genesis and development as well as the fundamental processes governing the interaction of tumors and their host tissues. We posit that these basic preclinical investigations will open up new and promising approaches to designing better therapies.

scholarly journals Role of Immune Escape Mechanisms in Hodgkin's Lymphoma Development and Progression: A Whole New World with Therapeutic Implications

2012 ◽  
Vol 2012 ◽  
pp. 1-24 ◽  
Author(s):  
Luis de la Cruz-Merino ◽  
Marylène Lejeune ◽  
Esteban Nogales Fernández ◽  
Fernando Henao Carrasco ◽  
Ana Grueso López ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Immune Escape ◽  
Hodgkin's Lymphoma ◽  
Young Population ◽  
Therapeutic Implications ◽  
Cell Components ◽  
Sizeable Fraction ◽  
Immune Escape Mechanisms ◽  
Lymphoproliferative Syndromes

Hodgkin's lymphoma represents one of the most frequent lymphoproliferative syndromes, especially in young population. Although HL is considered one of the most curable tumors, a sizeable fraction of patients recur after successful upfront treatment or, less commonly, are primarily resistant. This work tries to summarize the data on clinical, histological, pathological, and biological factors in HL, with special emphasis on the improvement of prognosis and their impact on therapeutical strategies. The recent advances in our understanding of HL biology and immunology show that infiltrated immune cells and cytokines in the tumoral microenvironment may play different functions that seem tightly related with clinical outcomes. Strategies aimed at interfering with the crosstalk between tumoral Reed-Sternberg cells and their cellular partners have been taken into account in the development of new immunotherapies that target different cell components of HL microenvironment. This new knowledge will probably translate into a change in the antineoplastic treatments in HL in the next future and hopefully will increase the curability rates of this disease.

PD1/PD-L1 Axis in Uro-oncology

2020 ◽  
Vol 21 (13) ◽  
pp. 1293-1300 ◽  
Author(s):  
Kerstin Junker ◽  
Markus Eckstein ◽  
Michelangelo Fiorentino ◽  
Rodolfo Montironi
Keyword(s):  
Tumor Cells ◽  
Standard Treatment ◽  
Immune Escape ◽  
Current Knowledge ◽  
Tumor Development ◽  
Immune Checkpoints ◽  
Urological Malignancies ◽  
Immune Therapies ◽  
Control Tumor ◽  
Immune Escape Mechanisms

The immune system is important to control tumor development and progression in humans. However, tumor cells and cells of the tumor microenvironment can induce immune escape mechanisms including activation of immune checkpoints such as PD-1/PD-L1. Based on this knowledge, new immune therapies, including PD-1 and PD-L1 inhibition, have been developed and are already recommended as a standard treatment in metastatic bladder and kidney cancer patients. In addition to its role as a therapeutic target, PD-L1 seems to be a prognostic parameter although data are controversial. Only little is known about signaling pathways inducing PD-L1 expression in tumor cells on one hand and about its functional role for tumor cells itself. However, the understanding of the complex biological function of PD-L1 will improve therapeutic options in urological malignancies. This review is giving an overview of the current knowledge concerning the PD-1/PD-L1 axis in urological tumors including bladder, kidney, prostate, testicular and penile cancer.

Prostate Cancer Progression and Surrounding Microenvironment

2006 ◽  
Vol 21 (2) ◽  
pp. 88-95 ◽  
Author(s):  
C. Alberti
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Immune Escape ◽  
Tumor Stem Cell ◽  
Cellular Interactions ◽  
Immune Mediated ◽  
Immune Escape Mechanisms

Bidirectional cellular interactions between prostate cancer and prostate or bone stroma are needed for local tumor growth and distant metastasis. The genetics of cancer cells is affected by the host microenvironment and, reciprocally, permanent gene expression changes occur in the stroma surrounding epithelial cancer cells. The immune-mediated micromilieu also affects the progression of prostate cancer; the role of the immune system in controlling the growth of prostate cancer cells is complex, with immune escape mechanisms prevailing over effective antitumor response. Moreover, tumor stem cell models to explain the origin and progression of prostate cancer require appropriate environmental conditions. On the basis of a review of the literature, this article aims to outline the recent advances in the elucidation of the molecular mechanisms underlying the interactions between prostate cancer and its microenvironment.

Role of Tumor Cell Immune Escape Mechanisms in Cytomegalovirus-Mediated Oncomodulation

ChemInform ◽  
2005 ◽  
Vol 36 (20) ◽  
Author(s):  
Jindrich Jr. Cinatl ◽  
Martin Scholz ◽  
Hans Wilhelm Doerr
Keyword(s):  
Tumor Cell ◽  
Immune Escape ◽  
Immune Escape Mechanisms
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