The Tumor Microenvironment: A Milieu Hindering and Obstructing Antitumor Immune Responses
15 May 2020
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Excellent article on how tumors not only evade the immune system but recruit various elements for their own benefit, and how exosomes can be used to remotely signal and suppress immune responses. The more the tumor grows the more it suppresses anti-tumor responses and the less accessible it becomes to the remaining functional T-cells etc, and the more it can release invasive metastatic cells in a feedback loop.
In relation to spike protein, both can use ROS, derived peroxynitrite, cytokines and many other factors to suppress and skew the immune response (see previous post https://www.biorxiv.org/content/10.1101/2021.04.16.440215v1.full).
âThe tumor microenvironment (TME) has a decisive role in tumor differentiation, epigenetics, dissemination, and immune evasion. In fact, the TME is a highly heterogeneous milieu consisting of different cell types and many abundant molecules produced and released by tumor cells, stromal cells, and immune cells. In this review, the TME will be discussed from the immunologist's point of view.
Concrete evidences support that both innate and adaptive immunity are involved in immune surveillance. This is referred to as the elimination phase and is reviewed elsewhere (1). If the transformed cells evade immune control during the elimination phase, tumors are formed. As tumor cells and its stroma progress, the immunosuppressive mechanisms increase in magnitude. Although tumor cells can be recognized and eliminated by the immune system, the tumor continues to grow (equilibrium phase) and escapes surveillance (escape phase) later. Lymphocytes including natural killer (NK) cells, CD8+ T cells and CD4+ helper T (Th) cells together with proinflammatory macrophages (M1) and dendritic cells from the anti-tumor immune responses while the heterogeneous population of myeloid-derived suppressor cells (MDSCs) and Foxp3+ regulatory T cells (Tregs) counteract tumor immunity. These cells are attracted and expanded by the tumor and its stroma to both control the present effector lymphocytes and to hamper the novo activation of tumor-reactive lymphocytes. Tumor cells evade the immune cells by a plethora mechanisms such as downregulation or loss of tumor antigens, releasing immunosuppressive extracellular vesicles including exosomes, releasing immunosuppressive molecules including IL-10 and transforming growth factor β (TGF-β), shedding soluble major histocompatibility complex (MHC)-I, loss of adhesion molecules such as ICAMI, developing resistance to apoptosis by upregulation of BCL-2 and other anti-apoptosis molecules, and overexpressing programmed death ligand 1 (PD-L1) as well as Fas ligand and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). Tumor-released molecules shape the TME and induce immunosuppression that debilitate robust antitumor immune responses.â
More:
https://www.frontiersin.org/articles/10.3389/fimmu.2020.00940/full