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 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 Exercise-Induced Changes in Tumor Growth via Tumor Immunity

Sports ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 46
Author(s):  
Polyxeni Spiliopoulou ◽  
Maria Gavriatopoulou ◽  
Efstathios Kastritis ◽  
Meletios Athanasios Dimopoulos ◽  
Gerasimos Terzis
Keyword(s):  
Immune System ◽  
Physical Exercise ◽  
Tumor Growth ◽  
Tumor Immunity ◽  
Immune Cells ◽  
Immune Cell ◽  
Tumor Development ◽  
Exercise Induced ◽  
Induced Changes

Immunity in the tumor microenvironment plays a central role in tumor development. Cytotoxic immune cells act against tumors, while tumors manage to trigger immunosuppressive mechanisms for defense. One bout of physical exercise acutely regulates the immune system inducing short-term redistribution of immune cells among body organs. Repeated acute immune cell mobilization with continuing exercise training results in long-term adaptations. These long-term exercise-induced changes in the immune system arise both in healthy and in diseased populations, including cancer patients. Recent preclinical studies indicate that physical exercise may have a positive impact on intra-tumoral immune cell processes, resulting in tumor suppression. This short narrative review describes the effect of physical exercise on tumor growth as detected via changes in tumor immunity. Research evidence shows that exercise may improve tumor-suppressive functions and may reduce tumor-progressive responses and mechanisms of immune cells, controlling tumor development. Specifically, it seems that exercise in rodents triggers shifts in tumor infiltration of macrophages, neutrophils, natural killer cells, cytotoxic and regulatory T lymphocytes, resulting in tumor suppression. These recent promising data suggest that physical exercise could be combined with anticancer immunotherapies, although exercise parameters like intensity, duration, and frequency need to be evaluated in more detail. More research is needed to investigate the effect of exercise in other immune cell subtypes and their possible connection with tumor growth, whilst information from human tumors is also required.

scholarly journals Cellular and Extracellular Components in Tumor Microenvironment and Their Application in Early Diagnosis of Cancers

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Rui Wei ◽  
Si Liu ◽  
Shutian Zhang ◽  
Li Min ◽  
Shengtao Zhu
Keyword(s):  
Tumor Microenvironment ◽  
Early Diagnosis ◽  
Immune Cells ◽  
Interstitial Fluid ◽  
Fluid Pressure ◽  
Early Diagnosis Of Cancer ◽  
Diagnosis Of Cancer ◽  
Chemical Factors ◽  
Physical And Chemical

Tumors are surrounded by complex environmental components, including blood and lymph vessels, fibroblasts, endothelial cells, immune cells, cytokines, extracellular vesicles, and extracellular matrix. All the stromal components together with the tumor cells form the tumor microenvironment (TME). In addition, extracellular physical and chemical factors, including extracellular pH, hypoxia, elevated interstitial fluid pressure, and fibrosis, are closely associated with tumor progression, metastasis, immunosuppression, and drug resistance. Cellular and extracellular components in TME contribute to nearly all procedures of carcinogenesis. By summarizing the recent work in this field, we make a comprehensive review on the role of cellular and extracellular components in the process of carcinogenesis and their potential application in early diagnosis of cancer. We hope that a systematic review of the diverse aspects of TME will help both research scientists and clinicians in this field.

scholarly journals Immuno-oncology: are TAM receptors in glioblastoma friends or foes?

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yunxiang Zhou ◽  
Yali Wang ◽  
Hailong Chen ◽  
Yanyan Xu ◽  
Yi Luo ◽  
...  
Keyword(s):  
Immune Cells ◽  
Tyrosine Kinases ◽  
Epithelial To Mesenchymal Transition ◽  
Tumor Development ◽  
Treatment Resistance ◽  
Primary Brain Tumor ◽  
Inflammatory Factors ◽  
Mesenchymal Transition ◽  
Tam Receptors ◽  
Underlying Mechanisms

AbstractTyro3, Axl, and Mertk (TAM) receptors are a subfamily of receptor tyrosine kinases. TAM receptors have been implicated in mediating efferocytosis, regulation of immune cells, secretion of inflammatory factors, and epithelial-to-mesenchymal transition in the tumor microenvironment, thereby serving as a critical player in tumor development and progression. The pro-carcinogenic role of TAM receptors has been widely confirmed, overexpression of TAM receptors is tied to tumor cells growth, metastasis, invasion and treatment resistance. Nonetheless, it is surprising to detect that inhibiting TAM signaling is not all beneficial in the tumor immune microenvironment. The absence of TAM receptors also affects anti-tumor immunity under certain conditions by modulating different immune cells, as the functional diversification of TAM signaling is closely related to tumor immunotherapy. Glioblastoma is the most prevalent and lethal primary brain tumor in adults. Although research regarding the crosstalk between TAM receptors and glioblastoma remains scarce, it appears likely that TAM receptors possess potential anti-tumor effects rather than portraying a total cancer-driving role in the context of glioblastoma. Accordingly, we doubt whether TAM receptors play a double-sided role in glioblastoma, and propose the Janus-faced TAM Hypothesis as a conceptual framework for comprehending the precise underlying mechanisms of TAMs. In this study, we aim to cast a spotlight on the potential multidirectional effects of TAM receptors in glioblastoma and provide a better understanding for TAM receptor-related targeted intervention.

scholarly journals Emerging Roles of Long Noncoding RNAs in Immuno-Oncology

2021 ◽  
Vol 9 ◽  
Author(s):  
Xin Wang ◽  
Xu Wang ◽  
Midie Xu ◽  
Weiqi Sheng
Keyword(s):  
Tumor Microenvironment ◽  
Chromatin Remodeling ◽  
Immune Cells ◽  
Tumor Development ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Cancer Development ◽  
Immune Recognition ◽  
Tumor Surveillance ◽  
Post Transcriptional Regulation

Long noncoding RNAs (lncRNAs), defined as ncRNAs no longer than 200 nucleotides, play an important role in cancer development. Accumulating research on lncRNAs offers a compelling new aspect of genome modulation, in which they are involved in chromatin remodeling, transcriptional and post-transcriptional regulation, and cross-talk with other nucleic acids. Increasing evidence suggests that lncRNAs reshape the tumor microenvironment (TME), which accounts for tumor development and progression. At the same time, the insightful findings on lncRNAs in immune recognition and evasion in tumor-infiltrating immune cells raise concerns with regard to immuno-oncology. In this review, we describe the essential characteristics of lncRNAs, elucidate functions of immune components engaged in tumor surveillance, and present some instructive examples in this new area.

scholarly journals Normalizing Tumor Microenvironment to Treat Cancer: Bench to Bedside to Biomarkers

2013 ◽  
Vol 31 (17) ◽  
pp. 2205-2218 ◽  
Author(s):  
Rakesh K. Jain
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Fluid Pressure ◽  
Predictive Biomarkers ◽  
Treatment Resistance ◽  
Blood Perfusion ◽  
Neurofibromatosis Type ◽  
Recurrent Glioblastoma ◽  
Antiangiogenic Agents ◽  
Lymphatic Vasculature

For almost four decades, my work has focused on one challenge: improving the delivery and efficacy of anticancer therapeutics. Working on the hypothesis that the abnormal tumor microenvironment—characterized by hypoxia and high interstitial fluid pressure—fuels tumor progression and treatment resistance, we developed an array of sophisticated imaging technologies and animal models as well as mathematic models to unravel the complex biology of tumors. Using these tools, we demonstrated that the blood and lymphatic vasculature, fibroblasts, immune cells, and extracellular matrix associated with tumors are abnormal, which together create a hostile tumor microenvironment. We next hypothesized that agents that induce normalization of the microenvironment can improve treatment outcome. Indeed, we demonstrated that judicious use of antiangiogenic agents—originally designed to starve tumors—could transiently normalize tumor vasculature, alleviate hypoxia, increase delivery of drugs and antitumor immune cells, and improve the outcome of various therapies. Our trials of antiangiogenics in patients with newly diagnosed and recurrent glioblastoma supported this concept. They revealed that patients whose tumor blood perfusion increased in response to cediranib survived 6 to 9 months longer than those whose blood perfusion did not increase. The normalization hypothesis also opened doors to treating various nonmalignant diseases characterized by abnormal vasculature, such as neurofibromatosis type 2. More recently, we discovered that antifibrosis drugs capable of normalizing the tumor microenvironment can improve the delivery and efficacy of nano- and molecular medicines. Our current efforts are directed at identifying predictive biomarkers and more-effective strategies to normalize the tumor microenvironment for enhancing anticancer therapies.

scholarly journals Tumor Microenvironment

Medicina ◽  
2019 ◽  
Vol 56 (1) ◽  
pp. 15 ◽  
Author(s):  
Borros Arneth
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Development ◽  
Tumor Vasculature ◽  
Cell Types ◽  
Cancer Associated Fibroblasts ◽  
Positive Health ◽  
Positive Health Outcomes ◽  
Uncontrolled Cell Proliferation ◽  
Significant Attention ◽  
Malignant Behavior

Background and Objectives: The tumor microenvironment has been widely implicated in tumorigenesis because it harbors tumor cells that interact with surrounding cells through the circulatory and lymphatic systems to influence the development and progression of cancer. In addition, nonmalignant cells in the tumor microenvironment play critical roles in all the stages of carcinogenesis by stimulating and facilitating uncontrolled cell proliferation. Aim: This study aims to explore the concept of the tumor microenvironment by conducting a critical review of previous studies on the topic. Materials and Methods: This review relies on evidence presented in previous studies related to the topic. The articles included in this review were obtained from different medical and health databases. Results and Discussion: The tumor microenvironment has received significant attention in the cancer literature, with a particular focus on its role in tumor development and progression. Previous studies have identified various components of the tumor microenvironment that influence malignant behavior and progression. In addition to malignant cells, adipocytes, fibroblasts, tumor vasculature, lymphocytes, dendritic cells, and cancer-associated fibroblasts are present in the tumor microenvironment. Each of these cell types has unique immunological capabilities that determine whether the tumor will survive and affect neighboring cells. Conclusion: The tumor microenvironment harbors cancer stem cells and other molecules that contribute to tumor development and progression. Consequently, targeting and manipulating the cells and factors in the tumor microenvironment during cancer treatment can help control malignancies and achieve positive health outcomes.

Normalization of tumor microvasculature basing on targeting and modulation of tumor microenvironment

Nanoscale ◽  
2021 ◽  
Author(s):  
Zhipeng Li ◽  
Fang Ning ◽  
Changduo Wang ◽  
Hongli Yu ◽  
Qingming Ma ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Development ◽  
Compressive Force ◽  
Tumor Vasculature ◽  
Angiogenic Factors ◽  
Tumor Microvasculature

Angiogenesis is an essential process for tumor development. Owing to imbalance of pro- and anti-angiogenic factors, the tumor vasculature possesses the characteristics of tortuous, hyperpermeable vessels and compressive force, resulting...

scholarly journals Interactions Between Anti-Angiogenic Therapy and Immunotherapy in Glioblastoma

2022 ◽  
Vol 11 ◽  
Author(s):  
Saket Jain ◽  
Eric J. Chalif ◽  
Manish K. Aghi
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Randomized Clinical Trials ◽  
Neutralizing Antibody ◽  
Tumor Vasculature ◽  
Tumor Evolution ◽  
Therapeutic Modalities ◽  
Angiogenic Therapy ◽  
T Cell Infiltration ◽  
Immunosuppressive Microenvironment

Glioblastoma is the most aggressive brain tumor with a median survival ranging from 6.2 to 16.7 months. The complex interactions between the tumor and the cells of tumor microenvironment leads to tumor evolution which ultimately results in treatment failure. Immunotherapy has shown great potential in the treatment of solid tumors but has been less effective in treating glioblastoma. Failure of immunotherapy in glioblastoma has been attributed to low T-cell infiltration in glioblastoma and dysfunction of the T-cells that are present in the glioblastoma microenvironment. Recent advances in single-cell sequencing have increased our understanding of the transcriptional changes in the tumor microenvironment pre and post-treatment. Another treatment modality targeting the tumor microenvironment that has failed in glioblastoma has been anti-angiogenic therapy such as the VEGF neutralizing antibody bevacizumab, which did not improve survival in randomized clinical trials. Interestingly, the immunosuppressed microenvironment and abnormal vasculature of glioblastoma interact in ways that suggest the potential for synergy between these two therapeutic modalities that have failed individually. Abnormal tumor vasculature has been associated with immune evasion and the creation of an immunosuppressive microenvironment, suggesting that inhibiting pro-angiogenic factors like VEGF can increase infiltration of effector immune cells into the tumor microenvironment. Remodeling of the tumor vasculature by inhibiting VEGFR2 has also been shown to improve the efficacy of PDL1 cancer immunotherapy in mouse models of different cancers. In this review, we discuss the recent developments in our understanding of the glioblastoma tumor microenvironment specially the tumor vasculature and its interactions with the immune cells, and opportunities to target these interactions therapeutically. Combining anti-angiogenic and immunotherapy in glioblastoma has the potential to unlock these therapeutic modalities and impact the survival of patients with this devastating cancer.

scholarly journals The Janus Face of Tumor Microenvironment Targeted by Immunotherapy

2019 ◽  
Vol 20 (17) ◽  
pp. 4320 ◽  
Author(s):  
Buoncervello ◽  
Gabriele ◽  
Toschi
Keyword(s):  
Tumor Microenvironment ◽  
T Lymphocytes ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Immune Cells ◽  
Antitumor Immunity ◽  
Therapeutic Response ◽  
Tumor Development ◽  
Response To Therapy ◽  
Cd8 T Lymphocytes

The tumor microenvironment (TME) is a complex entity where host immune and non-immune cells establish a dynamic crosstalk with cancer cells. Through cell-cell interactions, which are mediated by key signals, such as the PD-1/PD-L1 axis, as well as the release of soluble mediators, this articulated process defines the nature of TME determining tumor development, prognosis, and response to therapy. Specifically, tumors are characterized by cellular plasticity that allows for the microenvironment to polarize towards inflammation or immunosuppression. Thus, the dynamic crosstalk among cancer, stromal, and immune components crucially favors the dominance of one of the Janus-faced contexture of TME crucial to the outcome of tumor development and therapeutic response. However, mostly, TME is dominated by an immunosuppressive landscape that blocks antitumor immunity and sustain tumor progression. Hence, in most cases, the immunosuppressive components of TME are highly competent in suppressing tumor-specific CD8+ T lymphocytes, the effectors of cancer destruction. In this complex context, immunotherapy aims to arm the hidden Janus face of TME disclosing and potentiating antitumor immune signals. Herein, we discuss recent knowledge on the immunosuppressive crosstalk within TME, and share perspectives on how immunotherapeutic approaches may exploit tumor immune signals to generate antitumor immunity.

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