scholarly journals Latest Advances in Targeting the Tumor Microenvironment for Tumor Suppression

2019 ◽  
Vol 20 (19) ◽  
pp. 4719 ◽  
Author(s):  
Chloé Laplagne ◽  
Marcin Domagala ◽  
Augustin Le Naour ◽  
Christophe Quemerais ◽  
Dimitri Hamel ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Small Molecules ◽  
Tumor Development ◽  
Cell Types ◽  
Host Cells ◽  
Matrix Proteins ◽  
Cancer Cell Survival ◽  
Cancer Setting ◽  
Interfering Rna ◽  
Stromal Stem Cells

The tumor bulk is composed of a highly heterogeneous population of cancer cells, as well as a large variety of resident and infiltrating host cells, extracellular matrix proteins, and secreted proteins, collectively known as the tumor microenvironment (TME). The TME is essential for driving tumor development by promoting cancer cell survival, migration, metastasis, chemoresistance, and the ability to evade the immune system responses. Therapeutically targeting tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), regulatory T-cells (T-regs), and mesenchymal stromal/stem cells (MSCs) is likely to have an impact in cancer treatment. In this review, we focus on describing the normal physiological functions of each of these cell types and their behavior in the cancer setting. Relying on the specific surface markers and secreted molecules in this context, we review the potential targeting of these cells inducing their depletion, reprogramming, or differentiation, or inhibiting their pro-tumor functions or recruitment. Different approaches were developed for this targeting, namely, immunotherapies, vaccines, small interfering RNA, or small molecules.

scholarly journals CCL2: An Important Mediator Between Tumor Cells and Host Cells in Tumor Microenvironment

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiakang Jin ◽  
Jinti Lin ◽  
Ankai Xu ◽  
Jianan Lou ◽  
Chao Qian ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cell Types ◽  
Host Cells ◽  
Specific Cell ◽  
Tumor Patients ◽  
Multiple Tumor ◽  
Inflammatory Monocytes ◽  
Immunosuppressive Cell ◽  
Tumor Types

Tumor microenvironment (TME) formation is a major cause of immunosuppression. The TME consists of a considerable number of macrophages and stromal cells that have been identified in multiple tumor types. CCL2 is the strongest chemoattractant involved in macrophage recruitment and a powerful initiator of inflammation. Evidence indicates that CCL2 can attract other host cells in the TME and direct their differentiation in cooperation with other cytokines. Overall, CCL2 has an unfavorable effect on prognosis in tumor patients because of the accumulation of immunosuppressive cell subtypes. However, there is also evidence demonstrating that CCL2 enhances the anti-tumor capability of specific cell types such as inflammatory monocytes and neutrophils. The inflammation state of the tumor seems to have a bi-lateral role in tumor progression. Here, we review works focusing on the interactions between cancer cells and host cells, and on the biological role of CCL2 in these processes.

scholarly journals The Roles of Stroma-Derived Chemokine in Different Stages of Cancer Metastases

2020 ◽  
Vol 11 ◽  
Author(s):  
Shahid Hussain ◽  
Bo Peng ◽  
Mathew Cherian ◽  
Jonathan W. Song ◽  
Dinesh K. Ahirwar ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Tumor Development ◽  
Inflammatory Cells ◽  
Host Cells ◽  
Metastatic Niche ◽  
Cancer Pathogenesis ◽  
Cancer Metastases ◽  
Cellular Components

The intricate interplay between malignant cells and host cellular and non-cellular components play crucial role in different stages of tumor development, progression, and metastases. Tumor and stromal cells communicate to each other through receptors such as integrins and secretion of signaling molecules like growth factors, cytokines, chemokines and inflammatory mediators. Chemokines mediated signaling pathways have emerged as major mechanisms underlying multifaceted roles played by host cells during tumor progression. In response to tumor stimuli, host cells-derived chemokines further activates signaling cascades that support the ability of tumor cells to invade surrounding basement membrane and extra-cellular matrix. The host-derived chemokines act on endothelial cells to increase their permeability and facilitate tumor cells intravasation and extravasation. The tumor cells-host neutrophils interaction within the vasculature initiates chemokines driven recruitment of inflammatory cells that protects circulatory tumor cells from immune attack. Chemokines secreted by tumor cells and stromal immune and non-immune cells within the tumor microenvironment enter the circulation and are responsible for formation of a “pre-metastatic niche” like a “soil” in distant organs whereby circulating tumor cells “seed’ and colonize, leading to formation of metastatic foci. Given the importance of host derived chemokines in cancer progression and metastases several drugs like Mogamulizumab, Plerixafor, Repertaxin among others are part of ongoing clinical trial which target chemokines and their receptors against cancer pathogenesis. In this review, we focus on recent advances in understanding the complexity of chemokines network in tumor microenvironment, with an emphasis on chemokines secreted from host cells. We especially summarize the role of host-derived chemokines in different stages of metastases, including invasion, dissemination, migration into the vasculature, and seeding into the pre-metastatic niche. We finally provide a brief description of prospective drugs that target chemokines in different clinical trials against cancer.

scholarly journals Role of MSC in the Tumor Microenvironment

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2107 ◽  
Author(s):  
Ralf Hass
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Tumor Development ◽  
Tumor Stroma ◽  
Cell Types ◽  
Cellular Interactions ◽  
Cell Functions ◽  
Metastatic Behavior ◽  
Stem Cell Niches

The tumor microenvironment represents a dynamically composed matrix in which tissue-associated cancer cells are embedded together with a variety of further cell types to form a more or less separate organ-like structure. Constantly mutual interactions between cells of the tumor microenvironment promote continuous restructuring and growth in the tumor. A distinct organization of the tumor stroma also facilitates the formation of transient cancer stem cell niches, thereby contributing to progressive and dynamic tumor development. An important but heterogeneous mixture of cells that communicates among the cancer cells and the different tumor-associated cell types is represented by mesenchymal stroma-/stem-like cells (MSC). Following recruitment to tumor sites, MSC can change their functionalities, adapt to the tumor’s metabolism, undergo differentiation and synergize with cancer cells. Vice versa, cancer cells can alter therapeutic sensitivities and change metastatic behavior depending on the type and intensity of this MSC crosstalk. Thus, close cellular interactions between MSC and cancer cells can eventually promote cell fusion by forming new cancer hybrid cells. Consequently, newly acquired cancer cell functions or new hybrid cancer populations enlarge the plasticity of the tumor and counteract successful interventional strategies. The present review article highlights some important features of MSC within the tumor stroma.

scholarly journals Obesity-Related Fatty Acid and Cholesterol Metabolism in Cancer-Associated Host Cells

2020 ◽  
Vol 8 ◽  
Author(s):  
Ying Ye ◽  
Xiaoting Sun ◽  
Yongtian Lu
Keyword(s):  
Endothelial Cells ◽  
Fatty Acid ◽  
Tumor Microenvironment ◽  
Metabolic Regulation ◽  
Cholesterol Metabolism ◽  
Tumor Development ◽  
Host Cells ◽  
Acid Oxidation ◽  
Cancer Associated Fibroblasts ◽  
Future Perspectives

Obesity-derived disturbances in fatty acid and cholesterol metabolism are linked to numerous diseases, including various types of malignancy. In tumor cells, metabolic alterations have been long recognized and intensively studied. However, metabolic changes in host cells in the tumor microenvironment and their contribution to tumor development have been largely overlooked. During the last decade, research advances show that fatty acid oxidation, cholesterol metabolism, and lipid accumulation play critical roles in cancer-associated host cells such as endothelial cells, lymph endothelial cells, cancer-associated fibroblasts, tumor-associated myeloid cells, and tumor-associated lymphocytes. In addition to anti-angiogenic therapies and immunotherapy that have been practiced in the clinic, metabolic regulation is considered another promising cancer therapy targeting non-tumor host cells. Understanding the obesity-associated metabolism changes in cancer-associated host cells may ultimately be translated into therapeutic options that benefit cancer patients. In this mini-review, we briefly summarize the lipid metabolism associated with obesity and its role in host cells in the tumor microenvironment. We also discuss the current understanding of the molecular pathways involved and future perspectives to benefit from this metabolic complexity.

scholarly journals MicroRNAs: Their Role in Metabolism, Tumor Microenvironment, and Therapeutic Implications in Head and Neck Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5604
Author(s):  
Shine-Gwo Shiah ◽  
Sung-Tau Chou ◽  
Jang-Yang Chang
Keyword(s):  
Tumor Microenvironment ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Development ◽  
Cell Communication ◽  
Cell Types ◽  
Metabolic Reprogramming ◽  
Mesenchymal Transition ◽  
Therapeutic Implications ◽  
Rna Molecules ◽  
Non Coding Rna

MicroRNAs (miRNAs) are endogenous small non-coding RNA molecules that negatively regulate gene expression by binding to target mRNAs. Deregulated miRNAs can act as either oncogenic miRNAs or tumor suppressor miRNAs in controlling proliferation, differentiation, apoptosis, metastasis, epithelial–mesenchymal transition, and immune responses, which are all involved in the carcinogenesis process of HNSCC. Recent findings have shown that metabolic reprogramming is an important hallmark of cancer, which is necessary for malignant transformation and tumor development. Some reprogrammed metabolisms are believed to be required for HNSCC against an unfavorable tumor microenvironment (TME). The TME is composed of various cell types embedded in the altered extracellular matrix, among which exosomes, secreted by cancer cells, are one of the most important factors. Tumor-derived exosomes reshape the tumor microenvironment and play a crucial role in cell-to-cell communication during HNSCC development. Exosomes encapsulate many biomolecules, including miRNAs, circulate in body fluids, and can transmit intercellular regulatory messages to nearby and distant sites, which indicates that exosomal miRNAs have the potential to become non-invasive biomarkers. This review aims to clarify the functions of diverse miRNAs in HNSCC metabolic reprogramming and tumor-derived exosomes. In addition, it also emphasizes the potential role of miRNA as a biomarker in the diagnosis, prognosis, and treatment of HNSCC cancer.

scholarly journals Cancer: a mirrored room between tumor bulk and tumor microenvironment

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Pablo Hernández-Camarero ◽  
Elena López-Ruiz ◽  
Juan Antonio Marchal ◽  
Macarena Perán
Keyword(s):  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Tumor Development ◽  
Cell Types ◽  
Molecular Signature ◽  
Therapeutic Approaches ◽  
Metastatic Niche ◽  
Systematic Analysis ◽  
Tumor Mass ◽  
Functional Transformations

AbstractIt has been well documented that the tumor microenvironment (TME) plays a key role in the promotion of drug resistance, the support of tumor progression, invasiveness, metastasis, and even the maintenance of a cancer stem-like phenotype. Here, we reviewed TME formation presenting it as a reflection of a tumor’s own organization during the different stages of tumor development. Interestingly, functionally different groups of stromal cells seem to have specific spatial distributions within the TME that change as the tumor evolves into advanced stage progression which correlates with the fact that cancer stem-like cells (CSCs) are located in the edges of solid tumor masses in advanced tumors.We also focus on the continuos feedback that is established between a tumor and its surroundings. The “talk” between tumor mass cells and TME stromal cells, marks the evolution of both interlocuting cell types. For instance, the metabolic and functional transformations that stromal cells undergo due to tumor corrupting activity.Moreover, the molecular basis of metastatic spread is also approached, making special emphasis on the site-specific pre-metastatic niche formation as another reflection of the primary tumor molecular signature.Finally, several therapeutic approaches targeting primary TME and pre-metastatic niche are suggested. For instance, a systematic analysis of the TME just adjacent to the tumor mass to establish the proportion of myofibroblasts-like cancer-associated fibroblasts (CAFs) which may in turn correspond to stemness and metastases-promotion. Or the implementation of “re-education” therapies consisting of switching tumor-supportive stromal cells into tumor-suppressive ones. In summary, to improve our clinical management of cancer, it is crucial to understand and learn how to manage the close interaction between TME and metastasis.

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.

scholarly journals The Roles of Mesenchymal Stromal/Stem Cells in Tumor Microenvironment Associated with Inflammation

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Drenka Trivanović ◽  
Jelena Krstić ◽  
Ivana Okić Djordjević ◽  
Slavko Mojsilović ◽  
Juan Francisco Santibanez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Tumor Microenvironment ◽  
Tumor Tissue ◽  
Tumor Development ◽  
Antitumor Therapy ◽  
Delivery Vehicles ◽  
Stromal Stem Cells ◽  
Immunomodulatory Potential ◽  
Functional Phenotype

State of tumor microenvironment (TME) is closely linked to regulation of tumor growth and progression affecting the final outcome, refractoriness, and relapse of disease. Interactions of tumor, immune, and mesenchymal stromal/stem cells (MSCs) have been recognized as crucial for understanding tumorigenesis. Due to their outstanding features, stem cell-like properties, capacity to regulate immune response, and dynamic functional phenotype dependent on microenvironmental stimuli, MSCs have been perceived as important players in TME. Signals provided by tumor-associated chronic inflammation educate MSCs to alter their phenotype and immunomodulatory potential in favor of tumor-biased state of MSCs. Adjustment of phenotype to TME and acquisition of tumor-promoting ability by MSCs help tumor cells in maintenance of permissive TME and suppression of antitumor immune response. Potential utilization of MSCs in treatment of tumor is based on their inherent ability to home tumor tissue that makes them suitable delivery vehicles for immune-stimulating factors and vectors for targeted antitumor therapy. Here, we review data regarding intrusive effects of inflammatory TME on MSCs capacity to affect tumor development through modification of their phenotype and interactions with immune system.

scholarly journals Senescence and Immunoregulation in the Tumor Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Megan K. Ruhland ◽  
Elise Alspach
Keyword(s):  
Tumor Microenvironment ◽  
Immune Responses ◽  
Cancer Treatment ◽  
Immune Cells ◽  
Tumor Development ◽  
Cell Types ◽  
Therapeutic Strategies ◽  
Recent Developments ◽  
Secretory Phenotype ◽  
The Many

Immunotherapies have revolutionized cancer treatment, but despite the many lives that have been extended by these therapies many patients do not respond for reasons that are not well understood. The tumor microenvironment (TME) is comprised of heterogeneous cells that regulate tumor immune responses and likely influence immunotherapy response. Senescent (e.g., aged) stroma within the TME, and its expression of the senescence-associated secretory phenotype induces chronic inflammation that encourages tumor development and disease progression. Senescent environments also regulate the function of immune cells in ways that are decidedly protumorigenic. Here we discuss recent developments in senescence biology and the immunoregulatory functions of senescent stroma. Understanding the multitude of cell types present in the TME, including senescent stroma, will aid in the development of combinatorial therapeutic strategies to increase immunotherapy efficacy.

scholarly journals Natural Compounds as Metabolic Modulators of the Tumor Microenvironment

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3494
Author(s):  
Ana S. Dias ◽  
Luisa Helguero ◽  
Catarina R. Almeida ◽  
Iola F. Duarte
Keyword(s):  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Biological Activities ◽  
Tumor Development ◽  
Cell Types ◽  
Natural Compounds ◽  
Response To Therapy ◽  
Promising Strategy ◽  
Functional Features ◽  
Important Therapeutic Target

The tumor microenvironment (TME) is a heterogenous assemblage of malignant and non-malignant cells, including infiltrating immune cells and other stromal cells, together with extracellular matrix and a variety of soluble factors. This complex and dynamic milieu strongly affects tumor differentiation, progression, immune evasion, and response to therapy, thus being an important therapeutic target. The phenotypic and functional features of the various cell types present in the TME are largely dependent on their ability to adopt different metabolic programs. Hence, modulating the metabolism of the cells in the TME, and their metabolic crosstalk, has emerged as a promising strategy in the context of anticancer therapies. Natural compounds offer an attractive tool in this respect as their multiple biological activities can potentially be harnessed to ‘(re)-educate’ TME cells towards antitumoral roles. The present review discusses how natural compounds shape the metabolism of stromal cells in the TME and how this may impact tumor development and progression.

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