scholarly journals Targeting Tumor-Associated Macrophages in Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5318
Author(s):  
Amy J. Petty ◽  
Dwight H. Owen ◽  
Yiping Yang ◽  
Xiaopei Huang
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Invasion ◽  
Therapeutic Strategies ◽  
Invasion And Metastasis ◽  
Tumor Associated Macrophages ◽  
Leukocyte Population ◽  
Promote Tumor Growth ◽  
Tumor Growth And Metastasis ◽  
Poor Outcomes ◽  
Inhibitory Molecules

Tumor-associated macrophages (TAMs) represent the most abundant leukocyte population in most solid tumors and are greatly influenced by the tumor microenvironment. More importantly, these macrophages can promote tumor growth and metastasis through interactions with other cell populations within the tumor milieu and have been associated with poor outcomes in multiple tumors. In this review, we examine how the tumor microenvironment facilitates the polarization of TAMs. Additionally, we evaluate the mechanisms by which TAMs promote tumor angiogenesis, induce tumor invasion and metastasis, enhance chemotherapeutic resistance, and foster immune evasion. Lastly, we focus on therapeutic strategies that target TAMs in the treatments of cancer, including reducing monocyte recruitment, depleting or reprogramming TAMs, and targeting inhibitory molecules to increase TAM-mediated phagocytosis.

scholarly journals Role of Tumor-Associated Macrophages in Sarcomas

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1086
Author(s):  
Tomohiro Fujiwara ◽  
John Healey ◽  
Koichi Ogura ◽  
Aki Yoshida ◽  
Hiroya Kondo ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Tumor Microenvironment ◽  
Dominant Role ◽  
Tumor Associated Macrophages ◽  
Novel Treatment ◽  
Promote Tumor Growth ◽  
Elevated Expression ◽  
Tumor Growth And Metastasis ◽  
Sarcoma Cells

Sarcomas are complex tissues in which sarcoma cells maintain intricate interactions with their tumor microenvironment. Tumor-associated macrophages (TAMs) are a major component of tumor-infiltrating immune cells in the tumor microenvironment and have a dominant role as orchestrators of tumor-related inflammation. TAMs promote tumor growth and metastasis, stimulate angiogenesis, mediate immune suppression, and limit the antitumor activity of conventional chemotherapy and radiotherapy. Evidence suggests that the increased infiltration of TAMs and elevated expression of macrophage-related genes are associated with poor prognoses in most solid tumors, whereas evidence of this in sarcomas is limited. Based on these findings, TAM-targeted therapeutic strategies, such as inhibition of CSF-1/CSF-1R, CCL2/CCR2, and CD47/SIRPα, have been developed and are currently being evaluated in clinical trials. While most of the therapeutic challenges that target sarcoma cells have been unsuccessful and the prognosis of sarcomas has plateaued since the 1990s, several clinical trials of these strategies have yielded promising results and warrant further investigation to determine their translational benefit in sarcoma patients. This review summarizes the roles of TAMs in sarcomas and provides a rationale and update of TAM-targeted therapy as a novel treatment approach for sarcomas.

scholarly journals Tumor-associated macrophages: potential therapeutic strategies and future prospects in cancer

2021 ◽  
Vol 9 (1) ◽  
pp. e001341
Author(s):  
Chunxiao Li ◽  
Xiaofei Xu ◽  
Shuhua Wei ◽  
Ping Jiang ◽  
Lixiang Xue ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
Tumor Immunotherapy ◽  
Therapeutic Strategies ◽  
Preclinical Studies ◽  
Future Prospects ◽  
Tumor Associated Macrophages

Macrophages are the most important phagocytes in vivo. However, the tumor microenvironment can affect the function and polarization of macrophages and form tumor-associated macrophages (TAMs). Usually, the abundance of TAMs in tumors is closely associated with poor prognosis. Preclinical studies have identified important pathways regulating the infiltration and polarization of TAMs during tumor progression. Furthermore, potential therapeutic strategies targeting TAMs in tumors have been studied, including inhibition of macrophage recruitment to tumors, functional repolarization of TAMs toward an antitumor phenotype, and other therapeutic strategies that elicit macrophage-mediated extracellular phagocytosis and intracellular destruction of cancer cells. Therefore, with the increasing impact of tumor immunotherapy, new antitumor strategies to target TAMs are now being discussed.

scholarly journals IL-35 Regulates the Function of Immune Cells in Tumor Microenvironment

2021 ◽  
Vol 12 ◽  
Author(s):  
Kewei Liu ◽  
Ai Huang ◽  
Jun Nie ◽  
Jun Tan ◽  
Shijie Xing ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Immune Cells ◽  
Immune Checkpoint Blockade ◽  
Future Research ◽  
Barr Virus ◽  
Promote Tumor Growth ◽  
Epstein Barr ◽  
Mechanistic Basis ◽  
Tumor Growth And Metastasis

Interleukin-35 (IL-35) is a heterodimeric cytokine composed of Epstein-Barr virus-induced gene 3 (EBI3) and IL-12p35 that has recently been shown to play diverse and important roles in the tumor microenvironment (TME). Owing to its immunosuppressive activity and ability to promote tumor growth and progression, IL-35 is widely recognized as a key mediator of TME status. Immune cells are key mediators of diverse tumor-related phenotypes, and immunosuppressive cytokines such as IL-35 can promote tumor growth and metastasis in TME. These influences should be considered together. Since tumor immunotherapy based on immune checkpoint blockade remains ineffective in many patients due to tumoral resistance, a new target or efficacy enhancing factor is urgently needed. Suppressing IL-35 production and activity has been demonstrated as an effective factor that inhibits tumor cells viability, and further investigation of this cytokine is warranted. However, the mechanistic basis for IL-35-mediated regulation of immune cells in the TME remains to be fully clarified. In the present review, we explore the roles of IL-35 in regulating immune cells within the TME. In addition, we highlight IL-35 as a specific immunological target and discuss its possible relevance in the context of immunotherapy. Lastly, we sought to summarize potential future research directions that may guide the advancement of current understanding regarding the role of this important cytokine as a regulator of oncogenesis.

scholarly journals Theranostic Probes for Targeting Tumor Microenvironment: An Overview

2017 ◽  
Author(s):  
Musafar Gani Sikkandhar ◽  
Anu Maashaa Nedumaran ◽  
Roopa Ravichandar ◽  
Satnam Singh ◽  
Induja Santhakumar ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Nuclear Imaging ◽  
Future Perspective ◽  
Resonance Imaging ◽  
Invasion And Metastasis ◽  
Connective Tissues ◽  
Anticancer Drug Delivery ◽  
Promote Tumor Growth ◽  
Magnetic Resonance Imaging Mri

Long gone was the time when tumors were thought to be insular masses of cells, residing independently at specific sites in an organ. Now, researchers gradually realize that tumors interact with the extracellular matrix (ECM), blood vessels, connective tissues and immune cells in their environment, which is now known as the tumor microenvironment (TME). It is found that the interactions between tumors and their surrounding promote tumor growth, invasion and metastasis. The dynamics and diversity of TME cause the tumors to be heterogeneous and thus pose a challenge for cancer diagnosis, drug design and therapy. As TME is significant in enhancing tumor progression, it is vital to identify the different components in the TME. This review explores how different factors in the TME supply tumors with the required growth factors and signaling molecules to proliferate, invade and metastasis. We also examine the development of TME-targeted nanotheranostics over the recent years for cancer therapy, diagnosis and anticancer drug delivery system. This review further discusses the limitations and future perspective of nanoparticle based theranostics when used in combination with current imaging modalities like Optical Imaging, Magnetic Resonance Imaging (MRI) and Nuclear Imaging (PET and SPECT).

Tumor microenvironment acid-sensitive liposomes enhanced colorectal cancer therapy by acting on both tumor cells and cancer-associated fibroblasts

Nanoscale ◽  
2021 ◽  
Author(s):  
chenglei li ◽  
Zhaohuan Li ◽  
Xue Gong ◽  
Jianhao Liu ◽  
Tingyue Zheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Crucial Role ◽  
Tumor Invasion ◽  
Cancer Associated Fibroblasts ◽  
Invasion And Metastasis ◽  
Promising Strategy

Cancer-associated fibroblasts (CAFs) play a crucial role in facilitating tumor invasion and metastasis, which act as the “soils” in tumor microenvironment (TME). Accordingly, it would be a promising strategy to...

Tumor-Associated Macrophages as Potential Targets for Anti-Cancer Activity of Marine Invertebrate-Derived Compounds

2021 ◽  
Vol 27 ◽  
Author(s):  
Lyudmila S. Dolmatova ◽  
Igor Yu. Dolmatov
Keyword(s):  
Marine Invertebrates ◽  
Marine Invertebrate ◽  
Mechanisms Of Action ◽  
Tumor Associated Macrophages ◽  
Drug Candidates ◽  
Promote Tumor Growth ◽  
Anti Cancer ◽  
M1 Phenotype ◽  
Marine Compounds ◽  
Tumor Growth And Metastasis

: Tumor-associated macrophages (TAMs) are M2 phenotype dominant and promote tumor growth and metastasis. The new cancer treatment strategy includes TAM targeting and is aimed primarily at reprogramming TAMs toward the M1 phenotype or reducing the number and activity of M2 macrophages. Several marine invertebrate-derived drugs, combining efficacy and a low level of side effects, were approved for use in the cancer therapy. The mechanisms of action of some of them include TAM targeting. The review includes data showing immunomodulatory properties of these already approved anticancer drugs and drug candidates in clinical development which additionally incorporate data from screening studies of new substances from marine invertebrates. Based on screening data, the most promising marine compounds for cancer immunotherapy are supposed.

scholarly journals New Mechanisms of Tumor-Associated Macrophages on Promoting Tumor Progression: Recent Research Advances and Potential Targets for Tumor Immunotherapy

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Qiujun Guo ◽  
Zhichao Jin ◽  
Yuan Yuan ◽  
Rui Liu ◽  
Tao Xu ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Poor Prognosis ◽  
Antitumor Immunity ◽  
Tumor Associated Macrophages ◽  
Immune Microenvironment ◽  
Comprehensive Review ◽  
Tumor Immune Microenvironment ◽  
Blocking Factors ◽  
Macrophage Plasticity ◽  
Poor Outcomes

The majority of basic and clinical studies have shown a protumor function of tumor-associated macrophages (TAMs), which represent a large proportion of matrix cells. TAMs promote tumorigenesis, and their number is related to the malignancy degree and poor prognosis of many kinds of tumors. Macrophage plasticity makes it possible to change the tumor microenvironment and remodel antitumor immunity during cancer immunotherapy. Increasing numbers of studies have revealed the effects of TAMs on the tumor microenvironment, for example, via promotion of tumor growth and tumorigenesis and through an increase in the number of cancer stem cells or via facilitation of angiogenesis, lymphangiogenesis, and metastasis. Investigators also proposed tumor-immunological treatments targeting TAMs by inhibiting TAM recruitment and differentiation, by regulating TAM polarization, and by blocking factors and pathways associated with the protumor function of TAMs. This comprehensive review presents recent research on TAMs in relation to prediction of poor outcomes, remodeling of the tumor immune microenvironment, and immunological targeted therapies.

scholarly journals Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
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.

scholarly journals How Cells Communicate with Each Other in the Tumor Microenvironment: Suggestions to Design Novel Therapeutic Strategies in Cancer Disease

2021 ◽  
Vol 22 (5) ◽  
pp. 2550
Author(s):  
Roberto Zefferino ◽  
Claudia Piccoli ◽  
Sante Di Gioia ◽  
Nazzareno Capitanio ◽  
Massimo Conese
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Therapeutic Strategies ◽  
Invasion And Metastasis ◽  
Complex Interplay ◽  
Cancer Disease ◽  
Novel Therapeutic Strategies ◽  
Early Late ◽  
Novel Therapeutic

Connexin- and pannexin (Panx)-formed hemichannels (HCs) and gap junctions (GJs) operate an interaction with the extracellular matrix and GJ intercellular communication (GJIC), and on account of this they are involved in cancer onset and progression towards invasiveness and metastatization. When we deal with cancer, it is not correct to omit the immune system, as well as neglecting its role in resisting or succumbing to formation and progression of incipient neoplasia until the formation of micrometastasis, nevertheless what really occurs in the tumor microenvironment (TME), which are the main players and which are the tumor or body allies, is still unclear. The goal of this article is to discuss how the pivotal players act, which can enhance or contrast cancer progression during two important process: “Activating Invasion and Metastasis” and the “Avoiding Immune Destruction”, with a particular emphasis on the interplay among GJIC, Panx-HCs, and the purinergic system in the TME without disregarding the inflammasome and cytokines thereof derived. In particular, the complex and contrasting roles of Panx1/P2X7R signalosome in tumor facilitation and/or inhibition is discussed in regard to the early/late phases of the carcinogenesis. Finally, considering this complex interplay in the TME between cancer cells, stromal cells, immune cells, and focusing on their means of communication, we should be capable of revealing harmful messages that help the cancer growth and transform them in body allies, thus designing novel therapeutic strategies to fight cancer in a personalized manner.

scholarly journals Preclinical and Clinical Therapeutic Strategies Affecting Tumor-Associated Macrophages in Hepatocellular Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
H. Degroote ◽  
A. Van Dierendonck ◽  
A. Geerts ◽  
H. Van Vlierberghe ◽  
L. Devisscher
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cell ◽  
Therapeutic Agents ◽  
Therapeutic Strategies ◽  
Tumor Associated Macrophages ◽  
Underlying Liver Disease ◽  
Promote Tumor Growth ◽  
Promising Target ◽  
Anticancer Immunity ◽  
Stimulation Of

Hepatocellular carcinoma (HCC) most often develops in patients with underlying liver disease characterized by chronic nonresolving inflammation. Tumor-associated macrophages (TAMs) are one of the most abundant immune cell populations within the tumoral microenvironment. As key actors of cancer-related inflammation, they promote tumor growth by suppression of effective anticancer immunity, stimulation of angiogenesis, and tissue remodeling. Therefore, they have become an attractive and promising target for immunotherapy. The heterogeneity of TAM subtypes and their origin and dynamic phenotype during the initiation and progression of HCC has been partially unraveled and forms the base for the development of therapeutic agents. Current approaches are aimed at decreasing the population of TAMs by depleting macrophages present in the tumor, blocking the recruitment of bone marrow-derived monocytes, and/or functionally reprogramming TAMs to antitumoral behavior. In this review, the preclinical evolution and hitherto clinical trials for TAM-targeted therapy in HCC will be highlighted.

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