Role of the Immune Component of Tumor Microenvironment in the Efficiency of Cancer Treatment: Perspectives for the Personalized Therapy

2017 ◽  
Vol 23 (32) ◽  
pp. 4807-4826 ◽  
Author(s):  
Marina Stakheyeva ◽  
Vladimir Riabov ◽  
Irina Mitrofanova ◽  
Nikolai Litviakov ◽  
Evgeny Choynzonov ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Solid Tumors ◽  
Immune Cells ◽  
Critical Factor ◽  
Cancer Diagnostics ◽  
Patient Specific ◽  
Intratumor Heterogeneity ◽  
Therapeutic Approaches

Despite significant progress in cancer diagnostics and development of novel therapeutic regimens, successful treatment of advanced forms of cancer is still a challenge and may require personalized therapeutic approaches. In this review, we analyzed major mechanisms responsible for tumor cells chemoresistance and emphasized that intratumor heterogeneity is a critical factor that limits efficiency of cancer treatment. Intratumor heterogeneity is caused by genomic instability in cancer cells, resulting in the selection of resistant clones. Moreover, cancer cells in solid tumors are surrounded by cellular and molecular microenvironment that actively influences tumor cell behavior. Local tumor microenvironment (TME) consisting of immune cells with diverse phenotypes and functions strongly contributes to intratumor heterogeneity and modulates responses to treatment. Thus, targeting specific components of TME is a novel treatment strategy that can improve the outcome of conventional anti-cancer therapy. Here, we discuss modern immunotherapeutic approaches based on targeting tumorinfiltrating immune cells including neutrophils, dendritic cells, NK cells, T cells, B cells and macrophages. Among those, tumor-associated macrophages (TAM) that display a pronounced heterogeneity and phenotypic plasticity appear to be a major component in the TME of solid tumors, and emerge as perspective targets for cancer immunotherapy. TAM intratumor heterogeneity and the possible existence of patient-specific phenotype signature generate the basis for the development of individualized TAM-based therapeutic approaches.

scholarly journals When Cells Suffocate: Autophagy in Cancer and Immune Cells under Low Oxygen

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Katrin Schlie ◽  
Jaeline E. Spowart ◽  
Luke R. K. Hughson ◽  
Katelin N. Townsend ◽  
Julian J. Lum
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Patient Treatment ◽  
Low Oxygen ◽  
Tumor Environment ◽  
And Function ◽  
The Impact

Hypoxia is a signature feature of growing tumors. This cellular state creates an inhospitable condition that impedes the growth and function of all cells within the immediate and surrounding tumor microenvironment. To adapt to hypoxia, cells activate autophagy and undergo a metabolic shift increasing the cellular dependency on anaerobic metabolism. Autophagy upregulation in cancer cells liberates nutrients, decreases the buildup of reactive oxygen species, and aids in the clearance of misfolded proteins. Together, these features impart a survival advantage for cancer cells in the tumor microenvironment. This observation has led to intense research efforts focused on developing autophagy-modulating drugs for cancer patient treatment. However, other cells that infiltrate the tumor environment such as immune cells also encounter hypoxia likely resulting in hypoxia-induced autophagy. In light of the fact that autophagy is crucial for immune cell proliferation as well as their effector functions such as antigen presentation and T cell-mediated killing of tumor cells, anticancer treatment strategies based on autophagy modulation will need to consider the impact of autophagy on the immune system.

scholarly journals In Vitro Evaluation of CD276-CAR NK-92 Functionality, Migration and Invasion Potential in the Presence of Immune Inhibitory Factors of the Tumor Microenvironment

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1020
Author(s):  
Stefan Grote ◽  
Guillermo Ureña-Bailén ◽  
Kenneth Chun-Ho Chan ◽  
Caroline Baden ◽  
Markus Mezger ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Solid Tumors ◽  
Immune Cells ◽  
Immune Cell ◽  
Nk Cell ◽  
Migration And Invasion ◽  
Cellular Immunotherapy ◽  
Knock Out ◽  
Immunosuppressive Tumor Microenvironment

Background: Melanoma is the most lethal of all skin-related cancers with incidences continuously rising. Novel therapeutic approaches are urgently needed, especially for the treatment of metastasizing or therapy-resistant melanoma. CAR-modified immune cells have shown excellent results in treating hematological malignancies and might represent a new treatment strategy for refractory melanoma. However, solid tumors pose some obstacles for cellular immunotherapy, including the identification of tumor-specific target antigens, insufficient homing and infiltration of immune cells as well as immune cell dysfunction in the immunosuppressive tumor microenvironment (TME). Methods: In order to investigate whether CAR NK cell-based immunotherapy can overcome the obstacles posed by the TME in melanoma, we generated CAR NK-92 cells targeting CD276 (B7-H3) which is abundantly expressed in solid tumors, including melanoma, and tested their effectivity in vitro in the presence of low pH, hypoxia and other known factors of the TME influencing anti-tumor responses. Moreover, the CRISPR/Cas9-induced disruption of the inhibitory receptor NKG2A was assessed for its potential enhancement of NK-92-mediated anti-tumor activity. Results: CD276-CAR NK-92 cells induced specific cytolysis of melanoma cell lines while being able to overcome a variety of the immunosuppressive effects normally exerted by the TME. NKG2A knock-out did not further improve CAR NK-92 cell-mediated cytotoxicity. Conclusions: The strong cytotoxic effect of a CD276-specific CAR in combination with an “off-the-shelf” NK-92 cell line not being impaired by some of the most prominent negative factors of the TME make CD276-CAR NK-92 cells a promising cellular product for the treatment of melanoma and beyond.

scholarly journals Semaphorin Signaling in Cancer-Associated Inflammation

2019 ◽  
Vol 20 (2) ◽  
pp. 377 ◽  
Author(s):  
Giulia Franzolin ◽  
Luca Tamagnone
Keyword(s):  
Immune Response ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Disease Progression ◽  
Tumor Cells ◽  
Cross Talk ◽  
Immune Cells ◽  
Major Element ◽  
Inflammatory Cells ◽  
Anti Cancer

The inflammatory and immune response elicited by the growth of cancer cells is a major element conditioning the tumor microenvironment, impinging on disease progression and patients’ prognosis. Semaphorin receptors are widely expressed in inflammatory cells, and their ligands are provided by tumor cells, featuring an intense signaling cross-talk at local and systemic levels. Moreover, diverse semaphorins control both cells of the innate and the antigen-specific immunity. Notably, semaphorin signals acting as inhibitors of anti-cancer immune response are often dysregulated in human tumors, and may represent potential therapeutic targets. In this mini-review, we provide a survey of the best known semaphorin regulators of inflammatory and immune cells, and discuss their functional impact in the tumor microenvironment.

scholarly journals Towards the Immunogenic Hyperthermic Action: Modulated ElectroHyperthermia

2020 ◽  
pp. 1-6
Author(s):  
Andras Szasz ◽  
Andras Szasz
Keyword(s):  
Cancer Cells ◽  
Solid Tumors ◽  
Phase Ii ◽  
Immune Cells ◽  
Genetic Information ◽  
Clinical Applications ◽  
Clinical Use ◽  
Hyperthermia Treatment ◽  
Broad Perspective ◽  
Trade Name

Hyperthermia treatment for solid tumors is a long-used, but poorly accepted method in clinical use. Modulated electro-hyperthermia (mEHT, trade name: oncothermia®) changes the paradigm, introduces a novel, cellularly selective and immunogenic cell-ruination. The mEHT method produces tumor-vaccination, presenting the unharmed genetic information of cancer cells to immune cells [1]. The mEHT method is approved in more than 30 countries. Its phase II/III clinical applications indicate a broad perspective.

scholarly journals The Tumor Microenvironment of Epithelial Ovarian Cancer and Its Influence on Response to Immunotherapy

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 242 ◽  
Author(s):  
Galaxia Rodriguez ◽  
Kristianne Galpin ◽  
Curtis McCloskey ◽  
Barbara Vanderhyden
Keyword(s):  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Epithelial Ovarian Cancer ◽  
B Lymphocytes ◽  
Immune Cells ◽  
Ovarian Cancer Cell ◽  
Cell Types ◽  
Therapeutic Approaches ◽  
Mutational Burden ◽  
Tumor Mutational Burden

Immunotherapy as a treatment for cancer is a growing field of endeavor but reports of success have been limited for epithelial ovarian cancer. Overcoming the challenges to developing more effective therapeutic approaches lies in a better understanding of the factors in cancer cells and the surrounding tumor microenvironment that limit response to immunotherapies. This article provides an overview of some ovarian cancer cell features such as tumor-associated antigens, ovarian cancer-derived exosomes, tumor mutational burden and overexpression of immunoinhibitory molecules. Moreover, we describe relevant cell types found in epithelial ovarian tumors including immune cells (T and B lymphocytes, Tregs, NK cells, TAMs, MDSCs) and other components found in the tumor microenvironment including fibroblasts and the adipocytes in the omentum. We focus on how those components may influence responses to standard treatments or immunotherapies.

scholarly journals Blood and Cancer: Cancer Stem Cells as Origin of Hematopoietic Cells in Solid Tumor Microenvironments

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1293 ◽  
Author(s):  
Ghmkin Hassan ◽  
Masaharu Seno
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cancer Cells ◽  
Solid Tumor ◽  
Immune Cells ◽  
Hematopoietic Cells ◽  
Hematopoietic Stem ◽  
Tumor Microenvironments

The concepts of hematopoiesis and the generation of blood and immune cells from hematopoietic stem cells are some steady concepts in the field of hematology. However, the knowledge of hematopoietic cells arising from solid tumor cancer stem cells is novel. In the solid tumor microenvironment, hematopoietic cells play pivotal roles in tumor growth and progression. Recent studies have reported that solid tumor cancer cells or cancer stem cells could differentiate into hematopoietic cells. Here, we discuss efforts and research that focused on the presence of hematopoietic cells in tumor microenvironments. We also discuss hematopoiesis from solid tumor cancer stem cells and clarify the notion of differentiation of solid tumor cancer stem cells into non-cancer hematopoietic stem cells.

Nanoimmunotherapy – cloaked defenders to breach the cancer fortress

2018 ◽  
Vol 7 (4) ◽  
pp. 317-340 ◽  
Author(s):  
Gayathri Kandasamy ◽  
Vadim Annenkov ◽  
Uma Maheswari Krishnan
Keyword(s):  
Cancer Cells ◽  
Immune Cells ◽  
Immune Surveillance ◽  
Cancer Recurrence ◽  
Host Immune System ◽  
Therapeutic Approaches ◽  
Cytotoxic Effects ◽  
Cytotoxic Factor ◽  
Causes Of Mortality ◽  
Made In

AbstractCancer continues to be ranked among the top causes of mortality in the world despite the advances made in science and technology. The sub-par performance of cancer therapeutic strategies is due to the transformation of the cancer from a proliferating mass of cells into an impregnable fortress that manipulates and controls the microenvironment to prevent access to any potential cytotoxic factor as well as circumvent the innate immune surveillance processes. Recruitment of the native immune cells to selectively recognize and kill cancer cells can serve to augment the cytotoxic effects of conventional cancer therapeutic approaches. In addition to annihilation of the cancer cells, the induction of memory in the immune cells prevents the possibility of cancer recurrence. However, despite the apparent benefits of cancer immunotherapy, there are several pitfalls that need to be addressed in order to extend these benefits to the clinic. In this context, engineered nanostructured carrier systems can be effectively employed for an activation and priming of the host immune system selectively against the target cancer cells. This has led to the emergence of “nanoimmunotherapy” as an important therapeutic approach against cancer. The use of multi-functional nanomaterials in combination with immunotherapy offers possible solutions to overcome the current limitations in cancer therapy and represents the next generation of “smart therapeutics,” which forms the prime focus of discussion in this review.

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 Macrophages in Osteosarcoma Immune Microenvironment: Implications for Immunotherapy

2020 ◽  
Vol 10 ◽  
Author(s):  
Zhong-Wei Luo ◽  
Pan-Pan Liu ◽  
Zhen-Xing Wang ◽  
Chun-Yuan Chen ◽  
Hui Xie
Keyword(s):  
Overall Survival ◽  
Tumor Microenvironment ◽  
Bone Tumor ◽  
Immune Cells ◽  
Therapeutic Approaches ◽  
Immune Microenvironment ◽  
Primary Bone Tumor ◽  
Promising Strategy ◽  
Primary Bone ◽  
Malignant Primary Bone Tumor

Osteosarcoma is a malignant primary bone tumor commonly occurring in children and adolescents. The treatment of local osteosarcoma is mainly based on surgical resection and chemotherapy, whereas the improvement of overall survival remains stagnant, especially in recurrent or metastatic cases. Tumor microenvironment (TME) is closely related to the occurrence and development of tumors, and macrophages are among the most abundant immune cells in the TME. Due to their vital roles in tumor progression, macrophages have gained increasing attention as the new target of tumor immunotherapy. In this review, we present a brief overview of macrophages in the TME and highlight the clinical significance of macrophages and their roles in the initiation and progression of osteosarcoma. Finally, we summarize the therapeutic approaches targeting macrophage, which represent a promising strategy in osteosarcoma therapies.

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