Tumor immune microenvironment [Neurosurgery Wiki]

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====== Tumor immune microenvironment ======

The [[tumor]] [[microenvironment]] (TME) is the cellular [[environment]] in which the tumor exists, including surrounding [[blood vessel]]s, [[immune cell]]s, [[fibroblast]]s, bone marrow-derived inflammatory cells, [[lymphocyte]]s, [[signal]]ing molecules and the [[extracellular matrix]] (ECM).
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The [[tumor microenvironment]] (TME) could be simply characterized into cold (non T cell inflamed) or hot ([[T cell-inflamed tumor microenvironment]]), which is largely attributed to the levels of proinflammatory cytokine production and T cell infiltration
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With the advent of [[cancer immunotherapy]], there has been a major improvement in patients' [[quality of life]] and [[survival]]. The growth of cancer [[immunotherapy]] has dramatically changed our understanding of the basics of cancer biology and has altered the standards of [[care]] (surgery, radiotherapy, and chemotherapy) for patients. Cancer immunotherapy has generated significant excitement with the success of [[chimeric antigen receptor]] ([[CAR]]) [[T cell]] [[therapy]] in particular. Clinical results using CAR-T for hematological malignancies have led to the approval of four [[CD19]]-targeted and one [[B-cell]] maturation antigen (BCMA)-targeted cell therapy products by the US Food and Drug Administration ([[FDA]]). Also, [[immune checkpoint inhibitor]]s such as antibodies against Programmed Cell Death-1 ([[PD-1]]), Programmed Cell Death Ligand-1 ([[PD-L1]]), and Cytotoxic T-Lymphocyte-Associated Antigen 4 ([[CTLA-4]]) have shown promising therapeutic outcomes and long-lasting clinical effect in several tumor types and patients who are refractory to other treatments. Despite these promising results, the success of cancer immunotherapy in [[solid tumor]]s have been limited due to several barriers, which include [[immunosuppressive tumor microenvironment]] (TME), inefficient trafficking, and heterogeneity of [[tumor antigen]]s. This is further compounded by the high intra-tumoral pressure of solid tumors, which presents an additional challenge to successfully delivering treatments to solid tumors
((Guha P, Heatherton KR, O'Connell KP, Alexander IS, Katz SC. Assessing the [[Future]] of [[Solid Tumor]] [[Immunotherapy]]. Biomedicines. 2022 Mar 11;10(3):655. doi: 10.3390/biomedicines10030655. PMID: 35327456; PMCID: PMC8945484.)).
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The immunosuppressive [[tumor microenvironment]] (TME) of [[cancer]] strongly hinders the anti-tumor [[immune response]]s, thereby resulting in disappointing responses to [[immunotherapy]]. Chemoattractive and promotive traits of [[chemokine]]s exerted on [[leukocyte]]s have garnered interest in improving the efficiency of [[immunotherapy]] by increasing the infiltration of [[immune cell]]s in the TME. In a study, a [[folic acid]] (FA) -modified gene delivery system based on the self-assembly of DOTAP, MPEG-PCL-MPEG, and FA-PEG-PCL-PEG-FA, namely F-PPPD, was developed to deliver [[plasmid]]s encoding the immunostimulating chemokine [[CKb11]]. The delivery of plasmid CKb11 (pCKb11) by F-PPPD nanoparticles resulted in the high secretion of CKb11 from tumor cells, which successfully activated T cells, suppressed the M2 polarization of macrophages, promoted the maturation of [[dendritic cell]]s (DCs), facilitated the infiltration of [[natural killer cells]] and inhibited the infiltration of immunosuppressive cells in tumor tissues. Administration of F-PPPD/pCKb11 also significantly suppressed the cancer progression. The study demonstrated a [[nanotechnology]]-enabled delivery of pCKb11, that remodeled the immunosuppressive TME, for cancer treatment
((Nie W, Yu T, Liu X, Wang B, Li T, Wu Y, Zhou X, Ma L, Lin Y, Qian Z, Gao X. Non-viral vector mediated CKb11 with folic acid modification regulates macrophage polarization and DC maturation to elicit immune response against cancer. Bioact Mater. 2021 Apr 6;6(11):3678-3691. doi: 10.1016/j.bioactmat.2021.03.031. PMID: 33898872; PMCID: PMC8056185.)).

===== Glioma tumor immune microenvironment =====

see [[Glioma tumor immune microenvironment]].