scholarly journals Heterogeneous Myeloid Cells in Tumors

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3772
Author(s):  
Aixia Dou ◽  
Jing Fang
Keyword(s):  
Cancer Therapy ◽  
Tumor Cells ◽  
Cancer Biology ◽  
Clonal Evolution ◽  
Critical Role ◽  
Tumor Development ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
Main Function ◽  
Opposing Effects

Accumulating studies highlight a critical role of myeloid cells in cancer biology and therapy. The myeloid cells constitute the major components of tumor microenvironment (TME). The most studied tumor-associated myeloid cells (TAMCs) include monocytes, tumor-associated macrophages (TAMs), dendritic cells (DCs), cancer-related circulating neutrophils, tumor-associated neutrophils (TANs), and myeloid-derived suppressor cells (MDSCs). These heterogenous myeloid cells perform pro-tumor or anti-tumor function, exerting complex and even opposing effects on all stages of tumor development, such as malignant clonal evolution, growth, survival, invasiveness, dissemination and metastasis of tumor cells. TAMCs also reshape TME and tumor vasculature to favor tumor development. The main function of these myeloid cells is to modulate the behavior of lymphocytes, forming immunostimulatory or immunosuppressive TME cues. In addition, TAMCs play a critical role in modulating the response to cancer therapy. Targeting TAMCs is vigorously tested as monotherapy or in combination with chemotherapy or immunotherapy. This review briefly introduces the TAMC subpopulations and their function in tumor cells, TME, angiogenesis, immunomodulation, and cancer therapy.

scholarly journals Mechanisms and Functional Significance of Human Tumor-infiltrating Myeloid Cells

2019 ◽  
Vol 4 (2) ◽  
pp. 41-49
Author(s):  
Amin Ramezani ◽  
Fatemeh Sadat Toghraie
Keyword(s):  
Stromal Cells ◽  
Cancer Biology ◽  
Critical Role ◽  
Myeloid Cells ◽  
Human Tumor ◽  
Suppressor Cells ◽  
Myeloid Cell ◽  
Myeloid Derived Suppressor Cells ◽  
Patient Prognosis ◽  
Tumor Associated Neutrophils

Myeloid cells as the major components of tumor-infiltrating leukocytes play critical roles in anti-tumor immunity. However, emerging evidences have revealed that soluble factors produced by tumor/stromal cells skew myeloid cells toward a tumor-promoting phenotype. Tumor-infiltrating myeloid cells (TIMs) including tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), myeloid-derived suppressor cells (MDSCs), and tumor-associated dendritic cells (TADCs) are considered as the key mediators of tumor microenvironment (TME). TIMs have been shown to play important roles in various aspects of cancer biology and their presence is often linked to altered patient prognosis and survival. Regarding their critical role in TME, TIMs have been proposed as relevant targets of therapeutic strategies aimed at expanding immunostimulatory myeloid cell populations and depleting or modulating immunosuppressive ones. In this review, we briefly describe TIMs subsets and discuss the mechanisms by which TIMs induce immunosuppression, angiogenesis, and metastasis.

scholarly journals Urokinase-mediated recruitment of myeloid-derived suppressor cells and their suppressive mechanisms are blocked by MUC1/sec

Blood ◽  
2009 ◽  
Vol 113 (19) ◽  
pp. 4729-4739 ◽  
Author(s):  
Dan Ilkovitch ◽  
Diana M. Lopez
Keyword(s):  
Tumor Cells ◽  
Critical Role ◽  
Tumor Development ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Mucin 1 ◽  
Arginase 1 ◽  
Antitumor Properties ◽  
Tumor Expression

Abstract The transmembrane isoform of mucin 1 (MUC1/TM) is a well-recognized tumor antigen, contributing to tumorigenesis and immune evasion. Although MUC1/TM has been correlated with malignancy, we have previously reported on antitumor properties and prevention of tumor development by a secreted splice variant of MUC1 (MUC1/sec). Because myeloid-derived suppressor cells (MDSCs) play a critical role in tumor-induced immunosuppression, we investigated their recruitment by tumor cells expressing either MUC1/TM or MUC1/sec. DA-3 tumor cells expressing MUC1/sec recruit dramatically lower levels of MDSCs, relative to MUC1/TM-expressing DA-3 cells. Because MUC1/sec was previously shown to down-regulate tumor expression of urokinase plasminogen activator (uPA), a protease linked to tumor aggressiveness and metastasis, the potential role of uPA in MDSC recruitment was investigated. Tumor-derived uPA is capable of recruiting MDSCs, and correlates with tumor development. In addition to diminishing recruitment of MDSCs, the effect of MUC1/sec on MDSC-suppressive mechanisms was investigated. MUC1/sec, or its unique immunoenhancing peptide, is capable of blocking expression of arginase 1 and production of reactive oxygen species in MDSCs, implicated in the suppression of T cells. These findings demonstrate a new mechanism of MDSC recruitment, and provide evidence that MUC1/sec has antitumor properties affecting MDSCs.

scholarly journals Cellular context-dependent consequences of Apc mutations on gene regulation and cellular behavior

2017 ◽  
Vol 114 (4) ◽  
pp. 758-763 ◽  
Author(s):  
Kyoichi Hashimoto ◽  
Yosuke Yamada ◽  
Katsunori Semi ◽  
Masaki Yagi ◽  
Akito Tanaka ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Tumor Cells ◽  
Critical Role ◽  
Tumor Development ◽  
Cell Lineage ◽  
Genetic Rescue ◽  
Cellular Behavior ◽  
Cellular Context ◽  
Context Dependent

The spectrum of genetic mutations differs among cancers in different organs, implying a cellular context-dependent effect for genetic aberrations. However, the extent to which the cellular context affects the consequences of oncogenic mutations remains to be fully elucidated. We reprogrammed colon tumor cells in an ApcMin/+ (adenomatous polyposis coli) mouse model, in which the loss of the Apc gene plays a critical role in tumor development and subsequently, established reprogrammed tumor cells (RTCs) that exhibit pluripotent stem cell (PSC)-like signatures of gene expression. We show that the majority of the genes in RTCs that were affected by Apc mutations did not overlap with the genes affected in the intestine. RTCs lacked pluripotency but exhibited an increased expression of Cdx2 and a differentiation propensity that was biased toward the trophectoderm cell lineage. Genetic rescue of the mutated Apc allele conferred pluripotency on RTCs and enabled their differentiation into various cell types in vivo. The redisruption of Apc in RTC-derived differentiated cells resulted in neoplastic growth that was exclusive to the intestine, but the majority of the intestinal lesions remained as pretumoral microadenomas. These results highlight the significant influence of cellular context on gene regulation, cellular plasticity, and cellular behavior in response to the loss of the Apc function. Our results also imply that the transition from microadenomas to macroscopic tumors is reprogrammable, which underscores the importance of epigenetic regulation on tumor promotion.

Abstract 87: The Accumulation of Myeloid-derived Suppressor Cells Is a Compensatory Response to the Development of Hypertension

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Xiao Z Shen ◽  
Peng Shi ◽  
Jorge Giani ◽  
Ellen Bernstein ◽  
Kenneth E Bernstein
Keyword(s):  
Blood Pressure ◽  
T Cell ◽  
Angiotensin Ii ◽  
Critical Role ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Compensatory Response ◽  
Immunosuppressive Cell ◽  
Induced Hypertension

The immune system plays a critical role in the development of hypertension. The immune response consists of pro-inflammatory cells, but also immunosuppressive cells that reduce T cell function. An important category of natural immunosuppressive cell is myeloid-derived suppressor cells (MDSC). We now show that blood and spleen CD11b+ Gr1+ myeloid cells are elevated 2-fold in both angiotensin II and L-NAME induced hypertension. These increased myeloid cells are MDSC in that they elevate IL-4R expression and suppress T cell proliferation. When hypertensive mice were depleted of MDSC, using either anti-Gr1 antibody or gemcitabine, there was a 15 mmHg rise in blood pressure and aggravation of T cells activation with increased production of IFN-γ, TNFα and IL-17 in both spleen and kidney. In contrast, adoptive transfer of MDSC reduced blood pressure in angiotensin-II induced hypertension by 25 mmHg (see Figure). These data suggest a new concept, that the accumulation of MDSC is a compensatory response to the inflammation induced by hypertension. They also indicate that MDSC play an important role in regulating blood pressure.

scholarly journals Biological mechanisms linked to inflammation in cancer: Discovery of tumor microenvironment-related biomarkers and their clinical application in solid tumors

2020 ◽  
Vol 35 (1_suppl) ◽  
pp. 8-11 ◽  
Author(s):  
Paola Nisticò ◽  
Gennaro Ciliberto
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Tumor Development ◽  
Short Paper ◽  
Great Relevance ◽  
Cellular Components ◽  
The Relationship

Our view of cancer biology radically shifted from a “cancer-cell-centric” vision to a view of cancer as an organ disease. The concept that genetic and/or epigenetic alterations, at the basis of cancerogenesis, are the main if not the exclusive drivers of cancer development and the principal targets of therapy, has now evolved to include the tumor microenvironment in which tumor cells can grow, proliferate, survive, and metastasize only within a favorable environment. The interplay between cancer cells and the non-cellular and cellular components of the tumor microenvironment plays a fundamental role in tumor development and evolution both at the primary site and at the level of metastasis. The shape of the tumor cells and tumor mass is the resultant of several contrasting forces either pro-tumoral or anti-tumoral which have at the level of the tumor microenvironment their battle field. This crucial role of tumor microenvironment composition in cancer progression also dictates whether immunotherapy with immune checkpoint inhibitor antibodies is going to be efficacious. Hence, tumor microenvironment deconvolution has become of great relevance in order to identify biomarkers predictive of efficacy of immunotherapy. In this short paper we will briefly review the relationship between inflammation and cancer, and will summarize in 10 short points the key concepts learned so far and the open challenges to be solved.

Application of Nanocomposites in Cancer Immunotherapy

Nano LIFE ◽  
2017 ◽  
Vol 07 (03n04) ◽  
pp. 1750008
Author(s):  
Wenhan Liu ◽  
Zejun Wang ◽  
Yao Luo ◽  
Nan Chen
Keyword(s):  
Immune System ◽  
Cancer Therapy ◽  
Cancer Treatment ◽  
Cancer Immunotherapy ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Tumor Immunity ◽  
Critical Role ◽  
Clinical Advances ◽  
Review Current

Despite the clinical advances in oncology, cancer is still the major cause of death worldwide. Recent research demonstrates that the immune system plays a critical role in preventing tumor occurrence and development. The focus on cancer treatment has been shifted from directly targeting the tumor cells to motivating the immune system to achieve this goal. However, the activity of immune system is often suppressed in cancer patients. To boost the anti-tumor immunity against cancers, various nanocomposites have been developed to enhance the efficacy of immunostimulatory agents. Here, we review current advances in nanomaterial-mediated immunotherapy for the treatment of cancer, with an emphasis on applications of nanocomposites as immunoadjuvants in cancer therapy.

scholarly journals Myeloid Cells in the Tumor Microenvironment: Modulation of Tumor Angiogenesis and Tumor Inflammation

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Michael C. Schmid ◽  
Judith A. Varner
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Angiogenesis ◽  
Malignant Tumors ◽  
Critical Role ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
Myeloid Cell ◽  
Promote Tumor Growth ◽  
Bone Marrow Derived Cells

Myeloid cells are a heterogeneous population of bone marrow-derived cells that play a critical role during growth and metastasis of malignant tumors. Tumors exhibit significant myeloid cell infiltrates, which are actively recruited to the tumor microenvironment. Myeloid cells promote tumor growth by stimulating tumor angiogenesis, suppressing tumor immunity, and promoting metastasis to distinct sites. In this review, we discuss the role of myeloid cells in promoting tumor angiogenesis. Furthermore, we describe a subset of myeloid cells with immunosuppressive activity (known as myeloid-derived suppressor cells). Finally, we will comment on the mechanisms regulating myeloid cell recruitment to the tumor microenvironment and on the potential of myeloid cells as new targets for cancer therapy.

scholarly journals Immature myeloid cells directly contribute to skin tumor development by recruiting IL-17–producing CD4+ T cells

2015 ◽  
Vol 212 (3) ◽  
pp. 351-367 ◽  
Author(s):  
Myrna L. Ortiz ◽  
Vinit Kumar ◽  
Anna Martner ◽  
Sridevi Mony ◽  
Laxminarasimha Donthireddy ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Tumor Development ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
Tumor Formation ◽  
Skin Tumor ◽  
Cellular Mechanisms ◽  
Direct Role ◽  
Immature Myeloid Cells

Evidence links chronic inflammation with cancer, but cellular mechanisms involved in this process remain unclear. We have demonstrated that in humans, inflammatory conditions that predispose to development of skin and colon tumors are associated with accumulation in tissues of CD33+S100A9+ cells, the phenotype typical for myeloid-derived suppressor cells in cancer or immature myeloid cells (IMCs) in tumor-free hosts. To identify the direct role of these cells in tumor development, we used S100A9 transgenic mice to create the conditions for topical accumulation of these cells in the skin in the absence of infection or tissue damage. These mice demonstrated accumulation of granulocytic IMCs in the skin upon topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA), resulting in a dramatic increase in the formation of papillomas during epidermal carcinogenesis. The effect of IMCs on tumorigenesis was not associated with immune suppression, but with CCL4 (chemokine [C-C motif] ligand 4)-mediated recruitment of IL-17–producing CD4+ T cells. This chemokine was released by activated IMCs. Elimination of CD4+ T cells or blockade of CCL4 or IL-17 abrogated the increase in tumor formation caused by myeloid cells. Thus, this study implicates accumulation of IMCs as an initial step in facilitation of tumor formation, followed by the recruitment of CD4+ T cells.

scholarly journals The role of platelets in tumor cell metastasis

2021 ◽  
Vol 20 (4) ◽  
pp. 185-190
Author(s):  
A. A. Yakusheva ◽  
A. A. Filkova
Keyword(s):  
Tumor Cells ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Circulatory System ◽  
Main Function ◽  
Cell Metastasis ◽  
Inflammatory Processes ◽  
Extensive Experimental Data

Platelets are small, nuclear-free cells whose main function is to stop bleeding. In addition to performing a hemostatic function, platelets are also involved in immune and inflammatory processes. Extensive experimental data suggest that platelets support tumor metastasis and their activation plays a critical role in cancer progression. In the circulatory system, platelets protect tumor cells from immune elimination and promote their arrest at the endothelium, supporting the formation of secondary lesions. Due to the significant contribution of platelets to tumor cells survival and propagation, antithrombotic drugs are considered as a novel anti-metastasis approach. In this article, the authors set a goal to summarize and update the currently existing knowledge about the molecular mechanisms and the role of platelets-tumor cells interaction, as well as to discuss the possibility of platelets receptors as anti-metastasis targets. 

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