scholarly journals Dual Roles of Immune Cells and Their Factors in Cancer Development and Progression

2011 ◽  
Vol 7 (5) ◽  
pp. 651-658 ◽  
Author(s):  
Brian F. Zamarron ◽  
WanJun Chen
Keyword(s):  
Immune Cells ◽  
Cancer Development ◽  
Dual Roles

scholarly journals Leukocyte immunoglobulin-like receptor subfamily B: therapeutic targets in cancer

2021 ◽  
Vol 4 (1) ◽  
pp. 16-33
Author(s):  
Mi Deng ◽  
Heyu Chen ◽  
Xiaoye Liu ◽  
Ryan Huang ◽  
Yubo He ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Immune Evasion ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Cancer Biology ◽  
Cancer Development ◽  
Malignant Cells ◽  
Dual Roles ◽  
Anti Cancer ◽  
Therapeutic Development

Abstract Inhibitory leukocyte immunoglobulin-like receptors (LILRBs 1–5) transduce signals via intracellular immunoreceptor tyrosine-based inhibitory motifs that recruit phosphatases to negatively regulate immune activation. The activation of LILRB signaling in immune cells may contribute to immune evasion. In addition, the expression and signaling of LILRBs in cancer cells especially in certain hematologic malignant cells directly support cancer development. Certain LILRBs thus have dual roles in cancer biology—as immune checkpoint molecules and tumor-supporting factors. Here, we review the expression, ligands, signaling, and functions of LILRBs, as well as therapeutic development targeting them. LILRBs may represent attractive targets for cancer treatment, and antagonizing LILRB signaling may prove to be effective anti-cancer strategies.

scholarly journals From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2278
Author(s):  
Afshin Derakhshani ◽  
Zeinab Rostami ◽  
Hossein Safarpour ◽  
Mahdi Abdoli Shadbad ◽  
Niloufar Sadat Nourbakhsh ◽  
...  
Keyword(s):  
Single Cell ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cancer Development ◽  
Immune Checkpoints ◽  
Single Cell Sequencing ◽  
Increased Risk

Over the past decade, there have been remarkable advances in understanding the signaling pathways involved in cancer development. It is well-established that cancer is caused by the dysregulation of cellular pathways involved in proliferation, cell cycle, apoptosis, cell metabolism, migration, cell polarity, and differentiation. Besides, growing evidence indicates that extracellular matrix signaling, cell surface proteoglycans, and angiogenesis can contribute to cancer development. Given the genetic instability and vast intra-tumoral heterogeneity revealed by the single-cell sequencing of tumoral cells, the current approaches cannot eliminate the mutating cancer cells. Besides, the polyclonal expansion of tumor-infiltrated lymphocytes in response to tumoral neoantigens cannot elicit anti-tumoral immune responses due to the immunosuppressive tumor microenvironment. Nevertheless, the data from the single-cell sequencing of immune cells can provide valuable insights regarding the expression of inhibitory immune checkpoints/related signaling factors in immune cells, which can be used to select immune checkpoint inhibitors and adjust their dosage. Indeed, the integration of the data obtained from the single-cell sequencing of immune cells with immune checkpoint inhibitors can increase the response rate of immune checkpoint inhibitors, decrease the immune-related adverse events, and facilitate tumoral cell elimination. This study aims to review key pathways involved in tumor development and shed light on single-cell sequencing. It also intends to address the shortcomings of immune checkpoint inhibitors, i.e., their varied response rates among cancer patients and increased risk of autoimmunity development, via applying the data from the single-cell sequencing of immune cells.

scholarly journals IMUP and GPRC5A: Two Newly Identified Risk Score Indicators in Pancreatic Ductal Adenocarcinoma

2021 ◽  
Author(s):  
Rong Wei ◽  
Zixin Zeng ◽  
Ningning Shen ◽  
Ziyue Wang ◽  
Honghong Shen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Immune Cells ◽  
Cox Regression ◽  
Bioinformatic Analysis ◽  
Cancer Development ◽  
Local Hospital ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Key Genes ◽  
The Difference

Abstract Background Pancreatic cancer has been a threateningly lethal malignant tumor worldwide. Despite the promising survival improvement in other cancer types attributing to the fast development of molecular precise medicine, the current treatment situation of pancreatic cancer is still woefully challenging since its limited response to neither traditional radiotherapy and chemotherapy nor emerging immunotherapy. The study is to explore potential responsible genes during the development of pancreatic cancer, thus identifying promising gene indicators and probable drug targets. Methods Different bioinformatic analysis were used to interpret the genetic events in pancreatic cancer development. Firstly, based on multiple cDNA microarray profiles from Gene Expression Omnibus (GEO) database, the genes with differently mRNA expression in cancer comparing to normal pancreatic tissues were identified, followed by being grouped based on the difference level. Then, GO and KEGG were performed to separately interpret the multiple groups of genes, and further Kaplan-Meier survival and Cox Regression analysis assisted us to scale down the candidate genes and select the potential key genes. Further, the basic physicochemical properties, the association with immune cells infiltration, mutation or other types variations besides expression gap in pancreatic cancer comparing to normal tissues of the selected key genes were analyzed. Moreover, the aberrant changed expression of key genes was validated by immunohistochemistry (IHC) experiment using local hospital tissue microarray samples and the clinical significance was explored based on TCGA clinical data. Results Firstly, a total of 22491 genes were identified to express differently in cancer comparing to normal pancreatic tissues based on 5 cDNA expression profiles, and the difference of 487/22491 genes was over 8-fold, and 55/487 genes were shared in multi profiles. Moreover, after genes interpretation which showed the >8-fold genes were mainly related to extracellular matrix structural constituent regulation, Kaplan-Meier survival and Cox-regression analysis were performed continually, and the result indicated that of the 55 extracellular locating genes, GPRC5A and IMUP were the only two independent prognostic indicators of pancreatic cancer. Further, detailed information of IMUP and GPRC5A were analyzed including their physicochemical properties, their expression and variation ratio and their association with immune cells infiltration in cancer, as well as the probable signaling pathways of genes regulation on pancreatic cancer development. Lastly, local IHC experiment performed on PAAD tissue array which was produced with 64 local hospital patients samples confirmed that GPRC5A and IMUP were abnormally up-regulated in pancreatic cancer, which directly associated with worse patients both overall (OS) and recurrence free survival (RFS). Conclusions Using multiple bioinformatic analysis as well as local hospital samples validation, we revealed that GPRC5A and IMUP expression were abnormally up-regulated in pancreatic cancer which associated statistical significantly with patients survival, and the genes’ biological features and clinical significance were also explored. However, more detailed experiments and clinical trials are obligatory to support their further potential drug-target role in clinical medical treatment.

scholarly journals Old and New Players of Inflammation and Their Relationship With Cancer Development

2021 ◽  
Vol 11 ◽  
Author(s):  
Rodolfo Chavez-Dominguez ◽  
Mario Perez-Medina ◽  
Dolores Aguilar-Cazares ◽  
Miriam Galicia-Velasco ◽  
Manuel Meneses-Flores ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Equilibrium Phase ◽  
Dna Lesions ◽  
Cancer Development ◽  
Transformed Cells ◽  
Phagocytic Cells ◽  
Cancer Immunoediting ◽  
Molecular Patterns ◽  
Efficient Elimination

Pathogens or genotoxic agents continuously affect the human body. Acute inflammatory reaction induced by a non-sterile or sterile environment is triggered for the efficient elimination of insults that caused the damage. According to the insult, pathogen-associated molecular patterns, damage-associated molecular patterns, and homeostasis-altering molecular processes are released to facilitate the arrival of tissue resident and circulating cells to the injured zone to promote harmful agent elimination and tissue regeneration. However, when inflammation is maintained, a chronic phenomenon is induced, in which phagocytic cells release toxic molecules damaging the harmful agent and the surrounding healthy tissues, thereby inducing DNA lesions. In this regard, chronic inflammation has been recognized as a risk factor of cancer development by increasing the genomic instability of transformed cells and by creating an environment containing proliferation signals. Based on the cancer immunoediting concept, a rigorous and regulated inflammation process triggers participation of innate and adaptive immune responses for efficient elimination of transformed cells. When immune response does not eliminate all transformed cells, an equilibrium phase is induced. Therefore, excessive inflammation amplifies local damage caused by the continuous arrival of inflammatory/immune cells. To regulate the overstimulation of inflammatory/immune cells, a network of mechanisms that inhibit or block the cell overactivity must be activated. Transformed cells may take advantage of this process to proliferate and gradually grow until they become preponderant over the immune cells, preserving, increasing, or creating a microenvironment to evade the host immune response. In this microenvironment, tumor cells resist the attack of the effector immune cells or instruct them to sustain tumor growth and development until its clinical consequences. With tumor development, evolving, complex, and overlapping microenvironments are arising. Therefore, a deeper knowledge of cytokine, immune, and tumor cell interactions and their role in the intricated process will impact the combination of current or forthcoming therapies.

scholarly journals Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1946
Author(s):  
Yaroslav Teper ◽  
Guido Eibl
Keyword(s):  
Pancreatic Cancer ◽  
Immune Cells ◽  
Current Knowledge ◽  
Review Article ◽  
Cancer Development ◽  
Detailed Knowledge ◽  
Inflammatory Macrophages ◽  
Pancreatic Neoplasia ◽  
The Impact

Obesity is a known risk factor for the development of pancreatic cancer, one of the deadliest types of malignancies. In recent years it has become clear that the pancreatic microenvironment is critically involved and a contributing factor in accelerating pancreatic neoplasia. In this context obesity-associated chronic inflammation plays an important role. Among several immune cells, macrophages have been shown to contribute to obesity-induced tissue inflammation. This review article summarizes the current knowledge about the role of pancreatic macrophages in early pancreatic cancer development. It describes the heterogenous origin and mixture of pancreatic macrophages, their role in pancreatic endocrine and exocrine pathology, and the impact of obesity on islet and stromal macrophages. A model is postulated, by which during obesity monocytes are recruited into the pancreas, where they are polarized into pro-inflammatory macrophages that drive early pancreatic neoplasia. This occurs in the presence of local inflammatory, metabolic, and endocrine signals. A stronger appreciation and more detailed knowledge about the role of macrophages in early pancreatic cancer development will lead to innovative preventive or interceptive strategies.

scholarly journals Dual Roles for Immunity in Gastrointestinal Cancers

2010 ◽  
Vol 28 (26) ◽  
pp. 4045-4051 ◽  
Author(s):  
Cristina Ferrone ◽  
Glenn Dranoff
Keyword(s):  
Tumor Cell ◽  
Immune Cell ◽  
Expression Profiles ◽  
Cancer Development ◽  
Critical Event ◽  
Cytotoxic Lymphocytes ◽  
Prognostic Information ◽  
Dual Roles ◽  
Gastrointestinal Malignancies ◽  
Cancer Pathogenesis

Histopathologic examination reveals that most human tumors are associated with diverse immune cell infiltrates, but the roles of host reactions in disease pathogenesis and prognosis remain to be fully clarified. Recent investigations in genetically engineered murine tumor models have uncovered dual functions for immune responses during cancer development and progression. Alterations in tumor cell gene expression profiles and coding sequences may trigger the activation of cytotoxic lymphocytes, which act to restrain tumor growth. In contrast, persistent inflammatory reactions, which may be driven by infection, environmental toxins, or impaired immune regulation, create a microenvironment that fosters tumor cell growth, survival, invasion, and dissemination. The dynamic interplay of these competing responses appears to be a critical event in cancer pathogenesis, with tumor promotion and immune evasion proving dominant in clinically evident disease. Nonetheless, longitudinal studies of patient cohorts have demonstrated that particular histopathologic and genetic signatures of cytotoxic lymphocyte reactions provide important prognostic information. Here, we discuss the dual roles of immunity in cancer development, focusing on gastrointestinal malignancies, given the depth of recent insights into the mechanisms underlying these tumors.

Misprocessing and functional arrest of microRNAs by miR-Pirate: roles of miR-378 and miR-17

2013 ◽  
Vol 450 (2) ◽  
pp. 375-386 ◽  
Author(s):  
Zhaoqun Deng ◽  
Xiangling Yang ◽  
Ling Fang ◽  
Zina J. Rutnam ◽  
Burton B. Yang
Keyword(s):  
Mature Mirnas ◽  
Cancer Development ◽  
Seed Region ◽  
Dual Roles ◽  
Regulate Gene Expression ◽  
Transfected Cells ◽  
Repeat Sequences ◽  
Tumour Formation ◽  
Expression Construct ◽  
Non Coding Rnas

miRNAs (microRNAs) are short non-coding RNAs that can regulate gene expression in cancer development, which makes them valuable targets for therapeutic intervention. In the present study we report on an approach that can not only arrest the functions of mature miRNAs by binding to them, but it can also induce the ‘mis-processing’ of the target miRNA, producing a non-functional truncated miRNA. This approach involves generating an expression construct that produces an RNA fragment with 16 repeat sequences. The construct is named miR-Pirate (miRNA-interacting RNA-producing imperfect RNA and tangling endogenous miRNA). The transcript of the construct contained mismatches to the seed region, and thus it would not target the potential targets of the miRNA under study. The homology of the construct is sufficiently high, allowing the transcript to block miRNA functions. The functions of the construct were validated in cell cultures, in tumour formation assays and in transgenic mice stably expressing this construct. To explore the possibility of adopting this approach in gene therapy, we transfected cells with synthetic miR-Pirate and obtained the results we expected. The miR-Pirate, expressed by the construct or synthesized chemically, was found to be able to specifically pirate and silence a mature miRNA through its dual roles and thus could be clinically applied for miRNA intervention.

scholarly journals Tackling tumor microenvironment through epigenetic tools to improve cancer immunotherapy

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Iris Lodewijk ◽  
Sandra P. Nunes ◽  
Rui Henrique ◽  
Carmen Jerónimo ◽  
Marta Dueñas ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Immune Cells ◽  
Cancer Development ◽  
Main Body ◽  
Tumor Type ◽  
Epigenetic Alterations ◽  
Epigenetic Biomarkers ◽  
Epigenetic Machinery ◽  
The Impact

Abstract Background Epigenetic alterations are known contributors to cancer development and aggressiveness. Additional to alterations in cancer cells, aberrant epigenetic marks are present in cells of the tumor microenvironment, including lymphocytes and tumor-associated macrophages, which are often overlooked but known to be a contributing factor to a favorable environment for tumor growth. Therefore, the main aim of this review is to give an overview of the epigenetic alterations affecting immune cells in the tumor microenvironment to provoke an immunosuppressive function and contribute to cancer development. Moreover, immunotherapy is briefly discussed in the context of epigenetics, describing both its combination with epigenetic drugs and the need for epigenetic biomarkers to predict response to immune checkpoint blockage. Main body Combining both topics, epigenetic machinery plays a central role in generating an immunosuppressive environment for cancer growth, which creates a barrier for immunotherapy to be successful. Furthermore, epigenetic-directed compounds may not only affect cancer cells but also immune cells in the tumor microenvironment, which could be beneficial for the clinical response to immunotherapy. Conclusion Thus, modulating epigenetics in combination with immunotherapy might be a promising therapeutic option to improve the success of this therapy. Further studies are necessary to (1) understand in depth the impact of the epigenetic machinery in the tumor microenvironment; (2) how the epigenetic machinery can be modulated according to tumor type to increase response to immunotherapy and (3) find reliable biomarkers for a better selection of patients eligible to immunotherapy.

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