Crosstalk between cancer and immune cells: Role of tumor‐associated macrophages in the tumor microenvironment

Tumor-associated macrophages (TAMs) are one of the most abundant immune cells in the tumor microenvironment, and they play a pivotal role in prompting the various tumor growth. However, the role of TAMs in colorectal carcinoma (CRC) is controversial, because a few papers report that TAMs is beneficial to CRC patients. In this review, we discuss the good or bad roles of TAMs in CRC progression. Interestingly, recent studies provide strong evidence that TAMs facilitate CRC growth, but do not exert tumor suppressive activities. TAMs can stimulate CRC growth by altering extracellular matrix remodeling, tumor metabolism, angiogenesis, as well as the tumor microenvironment. Therefore, TAMs could serve as a target for CRC therapeutic treatment.

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circRNAs: Insight Into Their Role in Tumor-Associated Macrophages

Frontiers in Oncology ◽

10.3389/fonc.2021.780744 ◽

2021 ◽

Vol 11 ◽

Author(s):

Saili Duan ◽

Shan Wang ◽

Tao Huang ◽

Junpu Wang ◽

Xiaoqing Yuan

Keyword(s):

Drug Resistance ◽

Tumor Microenvironment ◽

Immune Cells ◽

Circular Rna ◽

Vital Role ◽

Stable Form ◽

Tumor Associated Macrophages ◽

Non Coding Rna ◽

Insight Into

Currently, it is well known that the tumor microenvironment not only provides energy support for tumor growth but also regulates tumor signaling pathways and promotes the proliferation, invasion, metastasis, and drug resistance of tumor cells. The tumor microenvironment, especially the function and mechanism of tumor-associated macrophages (TAMs), has attracted great attention. TAMs are the most common immune cells in the tumor microenvironment and play a vital role in the occurrence and development of tumors. circular RNA (circRNA) is a unique, widespread, and stable form of non-coding RNA (ncRNA), but little is known about the role of circRNAs in TAMs or how TAMs affect circRNAs. In this review, we summarize the specific manifestations of circRNAs that affect the tumor-associated macrophages and play a significant role in tumor progression. This review helps improve our understanding of the association between circRNAs and TAMs, thereby promoting the development and progress of potential clinical targeted therapies.

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The Role of Tumor-Associated Macrophages and Other Innate Immune Cells in Metastatic Progression of Lung Cancer

Lung Cancer Metastasis ◽

10.1007/978-1-4419-0772-1_11 ◽

2009 ◽

pp. 217-239

Author(s):

Zvi G. Fridlender ◽

M. Cecilia Crisanti ◽

Steven M. Albelda

Keyword(s):

Lung Cancer ◽

Immune Cells ◽

Innate Immune ◽

Innate Immune Cells ◽

Metastatic Progression ◽

Tumor Associated Macrophages

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The role of the hypoxia-Nrp-1 axis in the activation of M2-like tumor-associated macrophages in the tumor microenvironment of cervical cancer

Molecular Carcinogenesis ◽

10.1002/mc.22936 ◽

2018 ◽

Vol 58 (3) ◽

pp. 388-397 ◽

Cited By ~ 21

Author(s):

Xiao-Jing Chen ◽

Sha Wu ◽

Rui-Ming Yan ◽

Liang-Sheng Fan ◽

Lan Yu ◽

...

Keyword(s):

Cervical Cancer ◽

Tumor Microenvironment ◽

Tumor Associated Macrophages

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The Role of Tumor-Associated Macrophages in Leukemia

Acta Haematologica ◽

10.1159/000500315 ◽

2019 ◽

Vol 143 (2) ◽

pp. 112-117 ◽

Cited By ~ 2

Author(s):

Yueyang Li ◽

M. James You ◽

Yaling Yang ◽

Dongzhi Hu ◽

Chen Tian

Keyword(s):

Stem Cells ◽

Innate Immunity ◽

Mesenchymal Stem Cells ◽

Immune Cells ◽

Leukemia Cell ◽

Tumor Associated Macrophages ◽

Intrinsic Factors ◽

Different Types ◽

Tumor Growth And Metastasis

In addition to intrinsic factors, leukemia cell growth is influenced by the surrounding nonhematopoietic cells in the leukemic microenvironment, including fibroblasts, mesenchymal stem cells, vascular cells, and various immune cells. Despite the fact that macrophages are an important component of human innate immunity, tumor-associated macrophages (TAMs) have long been considered as an accomplice promoting tumor growth and metastasis. TAMs are activated by an abnormal malignant microenvironment, polarizing into a specific phenotype and participating in tumor progression. TAMs that exist in the microenvironment of different types of leukemia are called leukemia-associated macrophages (LAMs), which are reported to be associated with the progression of leukemia. This review describes the role of LAMs in different leukemia subtypes.

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Inflammatory Cells in Diffuse Large B Cell Lymphoma

Journal of Clinical Medicine ◽

10.3390/jcm9082418 ◽

2020 ◽

Vol 9 (8) ◽

pp. 2418

Author(s):

Roberto Tamma ◽

Girolamo Ranieri ◽

Giuseppe Ingravallo ◽

Tiziana Annese ◽

Angela Oranger ◽

...

Keyword(s):

Tumor Microenvironment ◽

B Cell ◽

Tumor Cells ◽

Immune Cells ◽

Tumor Antigens ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

Diffuse large B cell lymphoma (DLBCL), known as the most common non-Hodgkin lymphoma (NHL) subtype, is characterized by high clinical and biological heterogeneity. The tumor microenvironment (TME), in which the tumor cells reside, is crucial in the regulation of tumor initiation, progression, and metastasis, but it also has profound effects on therapeutic efficacy. The role of immune cells during DLBCL development is complex and involves reciprocal interactions between tumor cells, adaptive and innate immune cells, their soluble mediators and structural components present in the tumor microenvironment. Different immune cells are recruited into the tumor microenvironment and exert distinct effects on tumor progression and therapeutic outcomes. In this review, we focused on the role of macrophages, Neutrophils, T cells, natural killer cells and dendritic cells in the DLBCL microenvironment and their implication as target for DLBCL treatment. These new therapies, carried out by the induction of adaptive immunity through vaccination or passive of immunologic effectors delivery, enhance the ability of the immune system to react against the tumor antigens inducing the destruction of tumor cells.

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The Role of Tumor-Associated Macrophages in the Progression and Chemoresistance of Ovarian Cancer

Cells ◽

10.3390/cells9051299 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1299 ◽

Cited By ~ 2

Author(s):

Marek Nowak ◽

Magdalena Klink

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Immune Cells ◽

Ovarian Cancer Cells ◽

High Plasticity ◽

Tumor Associated Macrophages ◽

Survival Signaling ◽

High Level ◽

Stimulating Factor

Tumor-associated macrophages (TAMs) constitute the main population of immune cells present in the ovarian tumor microenvironment. These cells are characterized by high plasticity and can be easily polarized by colony-stimulating factor-1, which is released by tumor cells, into an immunosuppressive M2-like phenotype. These cells are strongly implicated in both the progression and chemoresistance of ovarian cancer. The main pro-tumoral function of M2-like TAMs is the secretion of a variety of cytokines, chemokines, enzymes and exosomes that reach microRNAs, directly inducing the invasion potential and chemoresistance of ovarian cancer cells by triggering their pro-survival signaling pathways. The M2-like TAMs are also important players in the metastasis of ovarian cancer cells in the peritoneum through their assistance in spheroid formation and attachment of cancer cells to the metastatic area—the omentum. Moreover, TAMs interplay with other immune cells, such as lymphocytes, natural killer cells, and dendritic cells, to inhibit their responsiveness, resulting in the development of immunosuppression. The detrimental character of the M2-like type of TAMs in ovarian tumors has been confirmed by a number of studies, demonstrating the positive correlation between their high level in tumors and low overall survival of patients.

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Tumor-Associated Neutrophils and Macrophages—Heterogenous but Not Chaotic

Frontiers in Immunology ◽

10.3389/fimmu.2020.553967 ◽

2020 ◽

Vol 11 ◽

Author(s):

Ling Wu ◽

Xiang H.-F. Zhang

Keyword(s):

Tumor Microenvironment ◽

Tumor Progression ◽

Cancer Cells ◽

Immune Cells ◽

Mutual Influence ◽

Therapeutic Resistance ◽

Tumor Associated Macrophages ◽

Tumor Associated Neutrophils ◽

Shed Light ◽

Lines Of Evidence

Tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) have been extensively studied. Their pleotropic roles were observed in multiple steps of tumor progression and metastasis, and sometimes appeared to be inconsistent across different studies. In this review, we collectively discussed many lines of evidence supporting the mutual influence between cancer cells and TAMs/TANs. We focused on how direct interactions among these cells dictate co-evolution involving not only clonal competition of cancer cells, but also landscape shift of the entire tumor microenvironment (TME). This co-evolution may take distinct paths and contribute to the heterogeneity of cancer cells and immune cells across different tumors. A more in-depth understanding of the cancer-TAM/TAN co-evolution will shed light on the development of TME that mediates metastasis and therapeutic resistance.

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The Inflammatory Microenvironment in Hepatocellular Carcinoma: A Pivotal Role for Tumor-Associated Macrophages

BioMed Research International ◽

10.1155/2013/187204 ◽

2013 ◽

Vol 2013 ◽

pp. 1-15 ◽

Cited By ~ 189

Author(s):

Daria Capece ◽

Mariafausta Fischietti ◽

Daniela Verzella ◽

Agata Gaggiano ◽

Germana Cicciarelli ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Growth Factors ◽

Tumor Microenvironment ◽

Cancer Cells ◽

Signaling Pathways ◽

Matrix Metalloproteases ◽

Pivotal Role ◽

M2 Macrophage ◽

Tumor Associated Macrophages

Hepatocellular carcinoma (HCC) is one of the most common and aggressive human cancers worldwide. HCC is an example of inflammation-related cancer and represents a paradigm of the relation occurring between tumor microenvironment and tumor development. Tumor-associated macrophages (TAMs) are a major component of leukocyte infiltrate of tumors and play a pivotal role in tumor progression of inflammation-related cancer, including HCC. Several studies indicate that, in the tumor microenvironment, TAMs acquire an M2-polarized phenotype and promote angiogenesis, metastasis, and suppression of adaptive immunity through the expression of cytokines, chemokines, growth factors, and matrix metalloproteases. Indeed, an established M2 macrophage population has been associated with poor prognosis in HCC. The molecular links that connect cancer cells and TAMs are not completely known, but recent studies have demonstrated that NF-κB, STAT-3, and HIF-1 signaling pathways play key roles in this crosstalk. In this paper, we discuss the current knowledge about the role of TAMs in HCC development, highlighting the role of TAM-derived cytokines, chemokines, and growth factors in the initiation and progression of liver cancer and outlining the signaling pathways involved in the interplay between cancer cells and TAMs.

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Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment

Mediators of Inflammation ◽

10.1155/2016/6058147 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 119

Author(s):

Jaehong Kim ◽

Jong-Sup Bae

Keyword(s):

Tumor Microenvironment ◽

Immune Cells ◽

Immune Surveillance ◽

Tumor Cell Invasion ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

Invasion And Metastasis ◽

Tumor Associated Macrophages ◽

Tumor Tissues ◽

Tumor Associated Neutrophils

Distinct tumor microenvironment forms in each progression step of cancer and has diverse capacities to induce both adverse and beneficial consequences for tumorigenesis. It is now known that immune cells can be activated to favor tumor growth and progression, most probably influenced by the tumor microenvironment. Tumor-associated macrophages and tumor-associated neutrophils can exert protumoral functions, enhancing tumor cell invasion and metastasis, angiogenesis, and extracellular matrix remodeling, while inhibiting the antitumoral immune surveillance. Considering that neutrophils in inflammatory environments recruit macrophages and that recruited macrophages affect neutrophil functions, there may be various degrees of interaction between tumor-associated macrophages and tumor-associated neutrophils. Platelets also play an important role in the recruitment and regulation of monocytic and granulocytic cells in the tumor tissues, suggesting that platelet function may be essential for generation of tumor-associated macrophages and tumor-associated neutrophils. In this review, we will explore the biology of tumor-associated macrophages and tumor-associated neutrophils and their possible interactions in the tumor microenvironment. Special attention will be given to the recruitment and activation of these tumor-associated cells and to the roles they play in maintenance of the tumor microenvironment and progression of tumors.

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