Nanomedicine-based cancer immunotherapies developed by reprogramming tumor-associated macrophages

Nanoscale ◽  
2021 ◽  
Author(s):  
Xiaoying Li ◽  
Xiaoming Guo ◽  
Jiabao Ling ◽  
Zheng Tang ◽  
Guanning Huang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factors ◽  
Tumor Microenvironment ◽  
Blood Vessels ◽  
Immune Cells ◽  
Tumor Development ◽  
Inflammatory Factors ◽  
Tumor Associated Macrophages ◽  
Complex Ecosystem ◽  
Cancer Immunotherapies

Tumor microenvironment is a complex ecosystem composed of tumor extracellular matrix, fibroblasts, blood vessels, and immune cells, promoting tumor development by secreting various growth factors, hydrolase, and inflammatory factors.

scholarly journals Toward Normalization of the Tumor Microenvironment for Cancer Therapy

2019 ◽  
Vol 18 ◽  
pp. 153473541986235 ◽  
Author(s):  
Jie Zheng ◽  
Peng Gao
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Normal Tissue ◽  
Cancer Growth ◽  
Tissue Architecture ◽  
Action Mechanisms ◽  
Anticancer Effects ◽  
Complex Ecosystem

The tumor microenvironment (TME) is a complex ecosystem, including blood vessels, immune cells, fibroblasts, extracellular matrix, cytokines, hormones, and so on. The TME differs from the normal tissue environment (NTE) in many aspects, such as tissue architecture, chronic inflammation, level of oxygen and pH, nutritional state of the cells, as well as tissue firmness. The NTE can inhibit the growth of cancer at the early tumorigenesis phase, whereas the TME promotes the growth of cancer in general, although it may have some anticancer effects. In particular, the TME plays a crucial role in the generation and maintenance of cancer stem cells, which lie at the root of cancer growth. Therefore, normalization of the TME to the NTE may inhibit cancer growth or improve cancer therapeutic efficiency. This review focuses on the recent emerging approaches for this normalization and the action mechanisms.

scholarly journals The Role of Tumor-Associated Macrophages in Colorectal Carcinoma Progression

2018 ◽  
Vol 45 (1) ◽  
pp. 356-365 ◽  
Author(s):  
Xiaoming Zhong ◽  
Bin Chen ◽  
Zhiwen Yang
Keyword(s):  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Colorectal Carcinoma ◽  
Tumor Growth ◽  
Immune Cells ◽  
Strong Evidence ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Tumor Associated Macrophages

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.

scholarly journals Tumor-Associated Neutrophils and Macrophages—Heterogenous but Not Chaotic

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.

scholarly journals The Immune Endocannabinoid System of the Tumor Microenvironment

2020 ◽  
Vol 21 (23) ◽  
pp. 8929
Author(s):  
Melanie Kienzl ◽  
Julia Kargl ◽  
Rudolf Schicho
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Immune Cells ◽  
Cannabinoid Receptors ◽  
Immune Cell ◽  
Tumor Development ◽  
Endocannabinoid System ◽  
Cell Functions ◽  
In Vitro Effects

Leukocytes are part of the tumor microenvironment (TME) and are critical determinants of tumor progression. Because of the immunoregulatory properties of cannabinoids, the endocannabinoid system (ECS) may have an important role in shaping the TME. Members of the ECS, an entity that consists of cannabinoid receptors, endocannabinoids and their synthesizing/degrading enzymes, have been associated with both tumor growth and rejection. Immune cells express cannabinoid receptors and produce endocannabinoids, thereby forming an “immune endocannabinoid system”. Although in vitro effects of exogenous cannabinoids on immune cells are well described, the role of the ECS in the TME, and hence in tumor development and immunotherapy, is still elusive. This review/opinion discusses the possibility that the “immune endocannabinoid system” can fundamentally influence tumor progression. The widespread influence of cannabinoids on immune cell functions makes the members of the ECS an interesting target that could support immunotherapy.

scholarly journals Cancer-Associated Fibroblast Heterogeneity: A Factor That Cannot Be Ignored in Immune Microenvironment Remodeling

2021 ◽  
Vol 12 ◽  
Author(s):  
Pei-Yu Chen ◽  
Wen-Fei Wei ◽  
Hong-Zhen Wu ◽  
Liang-Sheng Fan ◽  
Wei Wang
Keyword(s):  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Immune Regulation ◽  
Stromal Cells ◽  
Cancer Associated Fibroblasts ◽  
Immune Microenvironment ◽  
Cancer Associated Fibroblast ◽  
Different Origins ◽  
Fibroblast Heterogeneity

Cancer-associated fibroblasts (CAFs) are important, highly heterogeneous components of the tumor extracellular matrix that have different origins and express a diverse set of biomarkers. Different subtypes of CAFs participate in the immune regulation of the tumor microenvironment (TME). In addition to their role in supporting stromal cells, CAFs have multiple immunosuppressive functions, via membrane and secretory patterns, against anti-tumor immunity. The inhibition of CAFs function and anti-TME therapy targeting CAFs provides new adjuvant means for immunotherapy. In this review, we outline the emerging understanding of CAFs with a particular emphasis on their origin and heterogeneity, different mechanisms of their regulation, as well as their direct or indirect effect on immune cells that leads to immunosuppression.

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

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
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.

scholarly journals Role of Regular Physical Exercise in Tumor Vasculature: Favorable Modulator of Tumor Milieu

2020 ◽  
Author(s):  
Mário Esteves ◽  
Mariana P. Monteiro ◽  
Jose Alberto Duarte
Keyword(s):  
Tumor Microenvironment ◽  
Physical Exercise ◽  
Immune Cells ◽  
Fluid Pressure ◽  
Tumor Development ◽  
Tumor Vasculature ◽  
Vascular Conductance ◽  
Transient Nature ◽  
Underlying Mechanisms ◽  
Regular Physical Exercise

AbstractThe tumor vessel network has been investigated as a precursor of an inhospitable tumor microenvironment, including its repercussions in tumor perfusion, oxygenation, interstitial fluid pressure, pH, and immune response. Dysfunctional tumor vasculature leads to the extravasation of blood to the interstitial space, hindering proper perfusion and causing interstitial hypertension. Consequently, the inadequate delivery of oxygen and clearance of by-products of metabolism promote the development of intratumoral hypoxia and acidification, hampering the action of immune cells and resulting in more aggressive tumors. Thus, pharmacological strategies targeting tumor vasculature were developed, but the overall outcome was not satisfactory due to its transient nature and the higher risk of hypoxia and metastasis. Therefore, physical exercise emerged as a potential favorable modulator of tumor vasculature, improving intratumoral vascularization and perfusion. Indeed, it seems that regular exercise practice is associated with lasting tumor vascular maturity, reduced vascular resistance, and increased vascular conductance. Higher vascular conductance reduces intratumoral hypoxia and increases the accessibility of circulating immune cells to the tumor milieu, inhibiting tumor development and improving cancer treatment. The present paper describes the implications of abnormal vasculature on the tumor microenvironment and the underlying mechanisms promoted by regular physical exercise for the re-establishment of more physiological tumor vasculature.

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.

Cancer Immunology and Immuno-Oncology (Innate vs. Adaptive Cell Immunity)

2020 ◽  
Author(s):  
Nariman Nezami ◽  
Carlos J. Sanchez ◽  
John Moon ◽  
Jamil Shaikh ◽  
Nima Kokabi
Keyword(s):  
Immune System ◽  
Tumor Microenvironment ◽  
Tumor Metastasis ◽  
Tumor Development ◽  
Genetic Changes ◽  
Complex Interactions ◽  
Cell Immunity ◽  
Complex Ecosystem ◽  
Cellular Components

AbstractTumorigenesis occurs due to both intrinsic cellular genetic changes and imbalances within the tumor microenvironment. This microenvironment is composed of a complex ecosystem of tumor cells, vasculature, extracellular matrix, stromal cells, and immune cells. With these cells, there is both immune activation and immune suppression that promote or inhibit tumor development. These interactions lead to a constant flux of remodeling within the tumor microenvironment that additionally promote or inhibits tumor metastasis. To promote or suppress either antitumorigenic or protumorigenic effects, it is important to understand the complex interactions of the tumor and its interactions with the immune system within the tumor microenvironment. This review article addresses the role of the immune system and its cellular components within the tumor microenvironment.

scholarly journals Differential Polarization of Tumor-Associated Macrophages/Microglia Drives the Aggressiveness of Gliomas

2021 ◽  
Author(s):  
Nai-Wei Yao ◽  
Hsiu-Ting Lin ◽  
Ya-Lin Lin ◽  
Khamushavalli Geeviman ◽  
Fang Liao ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Wistar Rats ◽  
Tumor Development ◽  
C6 Glioma ◽  
Sprague Dawley ◽  
Tumor Associated Macrophages ◽  
Sd Rats ◽  
Glioma Growth

Abstract Background: Glioblastoma is the most aggressive subtype of brain tumors. The major component of tumor microenvironment in glioblastoma is tumor-associated macrophages (TAMs), which are associated with enhanced malignancy of glioblastoma. The polarization of macrophages to the pro-inflammatory M1 or anti-inflammatory M2 subtypes governed by the context of tumor microenvironment may dictate the aggressiveness and outcome of glioblastoma. Given that the immune responses to tumors vary distinctively among individuals due to intrinsic, environmental and genetic factors and that TAMs display a high level of diversity and plasticity, we aimed to examine the effects of differential polarization of TAMs on the glioblastoma development by implanting C6 glioma into brains of Sprague–Dawley (SD) and Wistar rats; these two rats have different genetic background and host microenvironment during tumor development. Methods: Sprague–Dawley (SD) and Wistar rats were implanted with C6 glioma in the brain. The measurement of tumor volumes, tumor morphology and tumor growth in C6 glioma implanted brains were measured by multi-parametric magnetic resonance imaging (MRI). Immunofluorescence staining was performed to analyze tumor angiogenesis and M1 and M2 TAMs in C6 gliomas. Results: By multi-parametric MRI measurement, C6 gliomas developed in the SD rats were characterized with enlarged tumors, accompanied with shorter animal survival. In comparison to the gliomas in Wistar rats, the accelerated tumor growth in SD rats was associated with greater extent of angiogenesis accompanied with higher levels of VEGF/VEGFR2. In support, C6 gliomas in SD rats were filtrated with TAMs characterized with a higher M2/M1 ratio, in contrast to the TAMs of a high M1/M2 ratio in Wistar rats. Attempts were made to shift the M2/M1 balance. Administration of the cytokine IFN-γ that induces M1 TAMs to SD rats greatly suppressed glioma formation, accompanied with a remarkable increase of M1 TAMs. Administration of the cytokines IL-4 plus IL-10 that induces M2 TAMs significantly promoted glioma growth in the Wistar rats, associated with an increase in the M2 TAMs. Conclusions: These results demonstrate an important role of TAMs in glioma pathogenesis and the crucial role of microenvironment in dictating the polarization of TAMs, suggesting that targeting or repolarization of TAMs may serve as an effective intervention for gliomas.

Sign in / Sign up

Export Citation Format

Share Document