Abstract
The heterogeneous tumor microenvironment is exceptionally perplexing and not wholly comprehended. Different multifaceted alignments lead to the generation of oxygen destitute situations within the tumor niche that modulate numerous intrinsic tumor microenvironments. Disentangling these communications is vital for scheming practical therapeutic approaches that can successfully decrease tumor allied chemotherapy resistance by utilizing the innate capability of the immune system. Several research groups are concerned with a protruding role for oxygen metabolism along with hypoxia in the immunity of healthy tissue. Hypoxia, in addition to hypoxia-inducible factors (HIFs) in the tumor microenvironment, plays an important part in tumor progression and endurance. Although numerous hypoxia-focused therapies have shown promising outcomes both in vitro and in vivo, these outcomes have not effectively translated into clinical preliminaries. Distinctive cell culture techniques have been utilized as an in vitro model for tumor niche along with tumor microenvironment and proficient in more precisely recreating tumor genomic profiles as well as envisaging therapeutic response. To study the dynamics of tumor immune evasion, three-dimensional (3D) cell cultures are more physiologically important to the hypoxic tumor microenvironment. Recent research has revealed new information and insights into our fundamental understanding of immune systems, and novel results that have been established as potential therapeutic targets. There are a lot of patented 3D cell culture techniques which will be highlighted in this review. At present notable 3D cell culture procedures in the hypoxic tumor microenvironment, discourse open doors to accommodate both drug repurposing, advancement, and divulgence of new medications and will deliberate the 3D cell culture methods into standard prescription disclosure, especially in the field of cancer biology, which will be discussing here.
Keywords: 3D cell culture, drug discovery, hypoxia, hypoxia-inducible factors, patent, tumor microenvironment, tumor-immune manifestations.
[http://dx.doi.org/10.1186/s12964-020-0530-4] [PMID: 32264958]
[http://dx.doi.org/10.1186/s13058-016-0740-2] [PMID: 27515302]
[http://dx.doi.org/10.1186/s12881-019-0767-1] [PMID: 30808328]
[http://dx.doi.org/10.2174/1566524020666200824103749] [PMID: 32838717]
[http://dx.doi.org/10.1615/CritRevImmunol.2020037044] [PMID: 33822523]
[http://dx.doi.org/10.1186/s40169-019-0226-9] [PMID: 30931508]
[http://dx.doi.org/10.1016/j.cell.2015.08.016] [PMID: 26321679]
[http://dx.doi.org/10.4161/cam.20377] [PMID: 22568985]
[http://dx.doi.org/10.1038/s41598-019-39476-9] [PMID: 30814616]
[http://dx.doi.org/10.1186/s40425-019-0556-6] [PMID: 30867051]
[http://dx.doi.org/10.3389/fphar.2018.00006] [PMID: 29410625]
[http://dx.doi.org/10.18632/oncotarget.26585] [PMID: 30774780]
[PMID: 30002710]
[http://dx.doi.org/10.1016/j.drudis.2012.10.003] [PMID: 23073387]
[http://dx.doi.org/10.3892/ol.2017.7134] [PMID: 29344128]
[http://dx.doi.org/10.1371/journal.pone.0059482] [PMID: 23527204]
[http://dx.doi.org/10.1016/j.semcancer.2005.05.002] [PMID: 15975824]
[http://dx.doi.org/10.1242/jcs.079509] [PMID: 22797912]
[http://dx.doi.org/10.1016/j.biomaterials.2012.08.061] [PMID: 22999468]
[http://dx.doi.org/10.1080/10463356.2010.11883480]
[http://dx.doi.org/10.1038/srep21174] [PMID: 26880118]
[http://dx.doi.org/10.1016/j.bbrc.2013.03.008] [PMID: 23501105]
[http://dx.doi.org/10.1038/nrm2236] [PMID: 17684528]
[http://dx.doi.org/10.1016/j.chembiol.2016.09.013] [PMID: 27984028]
[http://dx.doi.org/10.3390/ijms16035517] [PMID: 25768338]
[http://dx.doi.org/10.1093/jnci/djm135] [PMID: 17895480]
[http://dx.doi.org/10.1002/bit.22361] [PMID: 19472329]
[http://dx.doi.org/10.1177/1087057112456874] [PMID: 22923784]
[http://dx.doi.org/10.18632/oncotarget.10885] [PMID: 27486877]
[http://dx.doi.org/10.1038/nbt.3413] [PMID: 26878319]
[http://dx.doi.org/10.1016/j.biomaterials.2011.07.001] [PMID: 21782234]
[http://dx.doi.org/10.1016/j.bbrc.2012.09.059] [PMID: 23000157]
[http://dx.doi.org/10.1088/1758-5090/8/4/045005] [PMID: 27725343]
[http://dx.doi.org/10.1371/journal.pone.0077232] [PMID: 24194875]
[http://dx.doi.org/10.1089/adt.2014.573] [PMID: 24831787]
[http://dx.doi.org/10.1002/biot.201300492] [PMID: 25174503]
[http://dx.doi.org/10.1038/nprot.2008.226] [PMID: 19214182]
[http://dx.doi.org/10.1021/mp300595a] [PMID: 23461341]
[http://dx.doi.org/10.1038/nri2922] [PMID: 21469396]
[http://dx.doi.org/10.1513/AnnalsATS.201608-610MG]
[http://dx.doi.org/10.1016/j.jcmgh.2017.02.004] [PMID: 28462372]
[http://dx.doi.org/10.1186/s13046-020-01733-5] [PMID: 33109235]
[http://dx.doi.org/10.1038/s12276-019-0235-1] [PMID: 31221962]
[http://dx.doi.org/10.1186/1747-5341-4-2] [PMID: 19146696]
[http://dx.doi.org/10.1038/s41598-019-42836-0] [PMID: 31068603]
[http://dx.doi.org/10.1371/journal.pone.0217640] [PMID: 31150477]
[http://dx.doi.org/10.1177/1087057117696795] [PMID: 28520521]
[http://dx.doi.org/10.1016/j.apsb.2018.03.006] [PMID: 30258764]
[http://dx.doi.org/10.1016/j.heliyon.2020.e03719] [PMID: 32280802]
[http://dx.doi.org/10.1088/1758-5090/ab5158]
[http://dx.doi.org/10.1016/j.canlet.2017.03.006] [PMID: 28288873]
[PMID: 30320358]
[http://dx.doi.org/10.1016/j.tcb.2018.06.008] [PMID: 30041830]
[http://dx.doi.org/10.1371/journal.pone.0216564] [PMID: 31075118]
[http://dx.doi.org/10.1016/j.biomaterials.2013.11.038] [PMID: 24360576]
[http://dx.doi.org/10.1002/adbi.201700083] [PMID: 30221187]
[http://dx.doi.org/10.1007/978-1-62703-640-5_1] [PMID: 23975816]
[http://dx.doi.org/10.3390/ijms21176225] [PMID: 32872135]
[http://dx.doi.org/10.1038/s41598-017-06949-8] [PMID: 28751635]
[http://dx.doi.org/10.1038/s41598-017-04718-1] [PMID: 28663555]
[http://dx.doi.org/10.3791/2720] [PMID: 21587162]
[http://dx.doi.org/10.1089/adt.2010.0276] [PMID: 20662735]
[http://dx.doi.org/10.1016/j.bioactmat.2019.10.005] [PMID: 31709311]
[http://dx.doi.org/10.1186/s12935-020-01719-5] [PMID: 33472628]
[http://dx.doi.org/10.1186/s13046-017-0570-9] [PMID: 28774341]
[http://dx.doi.org/10.3390/ijms20092091] [PMID: 31035344]
[http://dx.doi.org/10.1016/j.canlet.2019.02.030] [PMID: 30790680]
[http://dx.doi.org/10.1038/nature05058] [PMID: 16871203]
[http://dx.doi.org/10.1186/s12938-020-0752-0] [PMID: 32050989]
[http://dx.doi.org/10.3390/ma11112199] [PMID: 30404222]
[http://dx.doi.org/10.1016/j.gendis.2017.10.002] [PMID: 29911158]
[PMID: 31249458]
[http://dx.doi.org/10.1186/s41100-019-0218-7]
[http://dx.doi.org/10.1007/s12195-018-0530-2] [PMID: 31719887]
[http://dx.doi.org/10.1016/j.addr.2018.06.011] [PMID: 29935988]
[http://dx.doi.org/10.1038/s41598-019-42439-9] [PMID: 30979929]
[http://dx.doi.org/10.3389/fcell.2019.00004] [PMID: 30761299]
[http://dx.doi.org/10.1002/prp2.454] [PMID: 30705757]
[http://dx.doi.org/10.1080/23723556.2018.1435184] [PMID: 30250892]
[http://dx.doi.org/10.1016/j.celrep.2018.12.090] [PMID: 30650355]
[http://dx.doi.org/10.1002/adhm.201900001] [PMID: 30734529]
[http://dx.doi.org/10.1016/j.actbio.2018.06.003] [PMID: 29879553]
[http://dx.doi.org/10.1016/j.biomaterials.2015.09.017] [PMID: 26402156]
[http://dx.doi.org/10.1371/journal.pone.0187314] [PMID: 29155844]
[http://dx.doi.org/10.1016/j.biomaterials.2010.07.064] [PMID: 20709389]
[http://dx.doi.org/10.1073/pnas.1015938108] [PMID: 21444794]
[http://dx.doi.org/10.1158/0008-5472.CAN-07-2225] [PMID: 18316601]
[http://dx.doi.org/10.1038/s41598-018-23250-4] [PMID: 29593247]
[http://dx.doi.org/10.1016/j.biomaterials.2011.10.056] [PMID: 22078807]
[http://dx.doi.org/10.1016/j.biomaterials.2014.03.003] [PMID: 24661550]
[http://dx.doi.org/10.1002/path.4778] [PMID: 27512948]
[http://dx.doi.org/10.1038/labinvest.2013.41] [PMID: 23459371]
[http://dx.doi.org/10.1016/j.biomaterials.2013.06.009] [PMID: 23827191]
[http://dx.doi.org/10.1016/j.biomaterials.2015.07.019] [PMID: 26196533]
[http://dx.doi.org/10.1016/j.biomaterials.2016.03.002] [PMID: 27116031]
[http://dx.doi.org/10.1016/j.molonc.2013.11.009] [PMID: 24388494]
[http://dx.doi.org/10.1016/j.jconrel.2014.12.039] [PMID: 25553823]
[http://dx.doi.org/10.1038/nature14415] [PMID: 25924068]
[http://dx.doi.org/10.2174/1566524020666201119143943] [PMID: 33213345]
[http://dx.doi.org/10.1016/j.neo.2014.12.004] [PMID: 25622895]
[http://dx.doi.org/10.1021/ac502269v] [PMID: 25118958]
[http://dx.doi.org/10.1039/c4ib00298a] [PMID: 25625883]
[http://dx.doi.org/10.1126/science.1188302] [PMID: 20576885]
[http://dx.doi.org/10.1371/journal.pone.0150044] [PMID: 26982031]
[http://dx.doi.org/10.1186/s12967-016-0855-3] [PMID: 27142386]
[http://dx.doi.org/10.1039/C2IB20209C] [PMID: 23172153]
[http://dx.doi.org/10.1126/scitranslmed.3003497] [PMID: 23136041]
[http://dx.doi.org/10.1039/C6IB00039H] [PMID: 27156572]
[http://dx.doi.org/10.2174/138920110792927757] [PMID: 20809896]
[http://dx.doi.org/10.1016/j.ab.2017.07.024] [PMID: 28757092]
[http://dx.doi.org/10.3389/fonc.2017.00293] [PMID: 29322028]
[http://dx.doi.org/10.3390/md16080279] [PMID: 30110923]