Insights into the Tumor Microenvironment—Components, Functions and Therapeutics

Abstract

Similarly to our healthy organs, the tumor tissue also constitutes an ecosystem. This implies that stromal cells acquire an altered phenotype in tandem with tumor cells, thereby promoting tumor survival. Cancer cells are fueled by abnormal blood vessels, allowing them to develop and proliferate. Tumor-associated fibroblasts adapt their cytokine and chemokine production to the needs of tumor cells and alter the peritumoral stroma by generating more collagen, thereby stiffening the matrix; these processes promote epithelial–mesenchymal transition and tumor cell invasion. Chronic inflammation and the mobilization of pro-tumorigenic inflammatory cells further facilitate tumor expansion. All of these events can impede the effective administration of tumor treatment; so, the successful inhibition of tumorous matrix remodeling could further enhance the success of antitumor therapy. Over the last decade, significant progress has been made with the introduction of novel immunotherapy that targets the inhibitory mechanisms of T cell activation. However, extensive research is also being conducted on the stromal components and other cell types of the tumor microenvironment (TME) that may serve as potential therapeutic targets.

The Copper Reduction Potential Determines the Reductive Cytotoxicity: Relevance to the Design of Metal–Organic Antitumor Drugs

“…In these situations, the oxidative damage of the plasma membrane emerges as a method of choice, since the necrotic mechanism remains functional in cells otherwise resistant to many chemotherapeutics [ 60 , 61 ]. Furthermore, the ROS-mediated elimination of tumor-associated stromal cells is therapeutically beneficial, because these species support tumor growth [ 62 , 63 ]. Our data suggest that ROS-induced salvation therapy upon Cu 2+ reduction would be useful in an advanced disease.…”

Development of Ex Vivo Analysis for Examining Cell Composition, Immunological Landscape, Tumor and Immune Related Markers in Non-small Cell Lung Cancer

“…As is known, the response to anti-NSCLC therapy, including immunotherapy, is a complex process in which factors related to TME heterogeneity have to be taken into account [34][35][36][37]. In this context, the immune cells, such as macrophages, lymphocytes, and others, in the TME might also have an impact on the tumor fate and, therefore, may serve as potential therapeutic targets to reinvigorate anti-tumor immunity [38,[40][41][42][43]56]. Furthermore, PD-L1 expression on the cancer cell membrane can be induced through the IFNγ and pro-inflammatory immune response [34].…”

“…Furthermore, PD-L1 expression on the cancer cell membrane can be induced through the IFNγ and pro-inflammatory immune response [34]. Tumorassociated macrophages are often divided into two sub-populations, showing either only antitumoral activity (classical activation with an M1-like phenotype and the expression of proinflammatory cytokines that activate adaptive immune response) or, conversely, only pro-tumoral activity (alternative activation with an M2-like phenotype and the expression of anti-inflammatory and immunosuppressive cytokines and growth factors that promote tumor survival and progression) [40][41][42][43]. However, now it is becoming clear that activation and polarization of tumor-associated macrophages may consist of a range of non-terminal phenotypes rather than two binary states [41].…”

“…Additionally, high tumor infiltrating T lymphocyte density associates directly with immunotherapy benefit in NSCLC patients and predicts clinical outcomes [34][35][36][37]. Therefore, deciphering the immune cell landscape and specific immune signatures of NSCLC is critical for improving the efficacy of the currently used immune checkpoint inhibitors [38][39][40] and designing next-generation immunomodulatory strategies addressing the immune microenvironment within tumors [41][42][43].…”

Melanoma-associated fibroblasts in tumor-promotion flammation and antitumor immunity: novel mechanisms and potential immunotherapeutic strategies

“…CAFs constitute a unique subset of fibroblasts within the tumor stroma, distinguished by their altered phenotype and functional characteristics induced by signals from cancer cells [ 4 ]. As orchestrators of the tumor microenvironment, CAFs contribute to various aspects of cancer progression [ 5 ]. They actively engage in extracellular matrix (ECM) remodeling, secrete a spectrum of growth factors, cytokines, and chemokines, and create a supportive niche for tumor cells [ 6 ].…”