{"id":"https://openalex.org/W7225613299","doi":"https://doi.org/10.3389/fimmu.2026.1935194","title":"Matrix stiffness in tumor immune evasion and immunotherapy resistance: from mechanotransduction to therapeutic intervention","display_name":"Matrix stiffness in tumor immune evasion and immunotherapy resistance: from mechanotransduction to therapeutic intervention","publication_year":2026,"publication_date":"2026-11-09","ids":{"openalex":"https://openalex.org/W7225613299","doi":"https://doi.org/10.3389/fimmu.2026.1935194"},"language":"en","primary_location":{"id":"doi:10.3389/fimmu.2026.1935194","doi":"https://doi.org/10.3389/fimmu.2026.1935194","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fimmu.2026.1935194","pdf_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1935194/pdf","source":{"id":"https://openalex.org/S2595292759","display_name":"Frontiers in Immunology","issn_l":"1664-3224","issn":["1664-3224"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Immunology","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1935194/pdf","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5100295863","display_name":"Wenwen Guo","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210145099","display_name":"Xian Yang Central Hospital","ror":"https://ror.org/042g3qa69","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210145099"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Wenwen Guo","raw_affiliation_strings":["Clinical Research Center, Xianyang Central Hospital"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Clinical Research Center, Xianyang Central Hospital","institution_ids":["https://openalex.org/I4210145099"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5067937852","display_name":"Tianyun Qiao","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Tianyun Qiao","raw_affiliation_strings":["Department of Thoracic Surgery, Air Force Hospital of Southern Theater Command"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Thoracic Surgery, Air Force Hospital of Southern Theater Command","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5067937852"],"corresponding_institution_ids":[],"apc_list":{"value":3150,"currency":"CHF","value_usd":3801},"apc_paid":{"value":3150,"currency":"CHF","value_usd":3801},"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.0,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"17","issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10379","display_name":"Cellular Mechanics and Interactions","score":0.9883000254631042,"subfield":{"id":"https://openalex.org/subfields/1307","display_name":"Cell Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10379","display_name":"Cellular Mechanics and Interactions","score":0.9883000254631042,"subfield":{"id":"https://openalex.org/subfields/1307","display_name":"Cell Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.00570000009611249,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11501","display_name":"TGF-\u03b2 signaling in diseases","score":0.0010000000474974513,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/extracellular-matrix-stiffness","display_name":"extracellular matrix stiffness","score":0.9660000205039978},{"id":"https://openalex.org/keywords/tumor-microenvironment","display_name":"tumor microenvironment","score":0.8889999985694885},{"id":"https://openalex.org/keywords/tumor-immune-evasion","display_name":"tumor immune evasion","score":0.890999972820282},{"id":"https://openalex.org/keywords/immunotherapy-resistance","display_name":"immunotherapy resistance","score":0.9589999914169312},{"id":"https://openalex.org/keywords/mechanotransduction","display_name":"mechanotransduction","score":0.9959999918937683},{"id":"https://openalex.org/keywords/cancer-associated-fibroblasts","display_name":"cancer-associated fibroblasts","score":0.8759999871253967},{"id":"https://openalex.org/keywords/lysyl-oxidase","display_name":"lysyl oxidase","score":0.8090000152587891},{"id":"https://openalex.org/keywords/collagen-deposition","display_name":"collagen deposition","score":0.9079999923706055},{"id":"https://openalex.org/keywords/tumor-associated-macrophages","display_name":"tumor-associated macrophages","score":0.8809999823570251},{"id":"https://openalex.org/keywords/m2-macrophage-polarization","display_name":"M2 macrophage polarization","score":0.8889999985694885},{"id":"https://openalex.org/keywords/tumor-associated-dendritic-cells","display_name":"tumor-associated dendritic cells","score":0.7319999933242798},{"id":"https://openalex.org/keywords/t-cell-exhaustion","display_name":"T cell exhaustion","score":0.824999988079071},{"id":"https://openalex.org/keywords/piezo1","display_name":"Piezo1","score":0.8009999990463257},{"id":"https://openalex.org/keywords/regulatory-t-cells","display_name":"regulatory T cells","score":0.8450000286102295},{"id":"https://openalex.org/keywords/pd-l1","display_name":"PD-L1","score":0.9409999847412109},{"id":"https://openalex.org/keywords/immune-checkpoint-blockade","display_name":"immune checkpoint blockade","score":0.7990000247955322},{"id":"https://openalex.org/keywords/cell-therapy","display_name":"cell therapy","score":0.4259999990463257}],"concepts":[{"id":"https://openalex.org/C181104049","wikidata":"https://www.wikidata.org/wiki/Q11936292","display_name":"Mechanotransduction","level":2,"score":0.8209999799728394},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.6266000270843506},{"id":"https://openalex.org/C189165786","wikidata":"https://www.wikidata.org/wiki/Q193825","display_name":"Extracellular matrix","level":2,"score":0.5795000195503235},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.5633999705314636},{"id":"https://openalex.org/C2776107976","wikidata":"https://www.wikidata.org/wiki/Q1786433","display_name":"Tumor microenvironment","level":3,"score":0.4948999881744385},{"id":"https://openalex.org/C2777701055","wikidata":"https://www.wikidata.org/wiki/Q1427096","display_name":"Immunotherapy","level":3,"score":0.45159998536109924},{"id":"https://openalex.org/C2780171871","wikidata":"https://www.wikidata.org/wiki/Q6804676","display_name":"Mechanobiology","level":2,"score":0.4438999891281128},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.438400000333786},{"id":"https://openalex.org/C77255625","wikidata":"https://www.wikidata.org/wiki/Q402093","display_name":"Reprogramming","level":3,"score":0.414900004863739},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.3783000111579895},{"id":"https://openalex.org/C2779244956","wikidata":"https://www.wikidata.org/wiki/Q184204","display_name":"Macrophage","level":3,"score":0.3747999966144562},{"id":"https://openalex.org/C136449434","wikidata":"https://www.wikidata.org/wiki/Q428253","display_name":"Innate immune system","level":3,"score":0.3686999976634979},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.36800000071525574},{"id":"https://openalex.org/C2780674031","wikidata":"https://www.wikidata.org/wiki/Q2012719","display_name":"Cancer immunotherapy","level":4,"score":0.35339999198913574},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3440999984741211},{"id":"https://openalex.org/C193419808","wikidata":"https://www.wikidata.org/wiki/Q1645075","display_name":"Acquired immune system","level":3,"score":0.3353999853134155},{"id":"https://openalex.org/C167672396","wikidata":"https://www.wikidata.org/wiki/Q417800","display_name":"CD8","level":3,"score":0.31470000743865967},{"id":"https://openalex.org/C2776682551","wikidata":"https://www.wikidata.org/wiki/Q21072584","display_name":"Macrophage polarization","level":4,"score":0.30869999527931213},{"id":"https://openalex.org/C106487976","wikidata":"https://www.wikidata.org/wiki/Q685816","display_name":"Matrix (chemical analysis)","level":2,"score":0.30090001225471497},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.28780001401901245},{"id":"https://openalex.org/C2776090121","wikidata":"https://www.wikidata.org/wiki/Q193529","display_name":"T cell","level":3,"score":0.28040000796318054},{"id":"https://openalex.org/C2776914184","wikidata":"https://www.wikidata.org/wiki/Q101991","display_name":"Inflammation","level":2,"score":0.271699994802475},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.27000001072883606},{"id":"https://openalex.org/C6929976","wikidata":"https://www.wikidata.org/wiki/Q3771881","display_name":"Regulator","level":3,"score":0.2680000066757202},{"id":"https://openalex.org/C2778170410","wikidata":"https://www.wikidata.org/wiki/Q506253","display_name":"Dendritic cell","level":3,"score":0.26660001277923584},{"id":"https://openalex.org/C2779341262","wikidata":"https://www.wikidata.org/wiki/Q182581","display_name":"Immunity","level":3,"score":0.2660999894142151},{"id":"https://openalex.org/C2778324207","wikidata":"https://www.wikidata.org/wiki/Q4733063","display_name":"Alloimmunity","level":3,"score":0.2637999951839447},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.25920000672340393},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.2581000030040741},{"id":"https://openalex.org/C127561419","wikidata":"https://www.wikidata.org/wiki/Q224527","display_name":"Downregulation and upregulation","level":3,"score":0.2533000111579895}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.3389/fimmu.2026.1935194","doi":"https://doi.org/10.3389/fimmu.2026.1935194","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fimmu.2026.1935194","pdf_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1935194/pdf","source":{"id":"https://openalex.org/S2595292759","display_name":"Frontiers in Immunology","issn_l":"1664-3224","issn":["1664-3224"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Immunology","raw_type":"journal-article"}],"best_oa_location":{"id":"doi:10.3389/fimmu.2026.1935194","doi":"https://doi.org/10.3389/fimmu.2026.1935194","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fimmu.2026.1935194","pdf_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1935194/pdf","source":{"id":"https://openalex.org/S2595292759","display_name":"Frontiers in Immunology","issn_l":"1664-3224","issn":["1664-3224"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Immunology","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.9537000060081482,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7225613299.pdf","grobid_xml":"https://content.openalex.org/works/W7225613299.grobid-xml"},"referenced_works_count":99,"referenced_works":["https://openalex.org/W1967359088","https://openalex.org/W1978577068","https://openalex.org/W1979281121","https://openalex.org/W1996912024","https://openalex.org/W2012884980","https://openalex.org/W2033998652","https://openalex.org/W2037342985","https://openalex.org/W2044895919","https://openalex.org/W2052186210","https://openalex.org/W2054635074","https://openalex.org/W2055801606","https://openalex.org/W2067319054","https://openalex.org/W2088110734","https://openalex.org/W2088812649","https://openalex.org/W2097969181","https://openalex.org/W2099052265","https://openalex.org/W2100044667","https://openalex.org/W2100303404","https://openalex.org/W2101728107","https://openalex.org/W2102498455","https://openalex.org/W2103883318","https://openalex.org/W2104479723","https://openalex.org/W2110344693","https://openalex.org/W2125150261","https://openalex.org/W2127119044","https://openalex.org/W2131381643","https://openalex.org/W2134208433","https://openalex.org/W2135139969","https://openalex.org/W2146337514","https://openalex.org/W2159855032","https://openalex.org/W2161349414","https://openalex.org/W2163629353","https://openalex.org/W2167961835","https://openalex.org/W2171157655","https://openalex.org/W2187985754","https://openalex.org/W2206971126","https://openalex.org/W2469223980","https://openalex.org/W2536479277","https://openalex.org/W2581595789","https://openalex.org/W2582686270","https://openalex.org/W2593027881","https://openalex.org/W2748062037","https://openalex.org/W2758838459","https://openalex.org/W2772923107","https://openalex.org/W2774142922","https://openalex.org/W2783271194","https://openalex.org/W2783370150","https://openalex.org/W2786027394","https://openalex.org/W2789880064","https://openalex.org/W2793869682","https://openalex.org/W2809059040","https://openalex.org/W2890611413","https://openalex.org/W2904712055","https://openalex.org/W2905196282","https://openalex.org/W2915186433","https://openalex.org/W2920302920","https://openalex.org/W2921063634","https://openalex.org/W2943229766","https://openalex.org/W2947955936","https://openalex.org/W2969551943","https://openalex.org/W2972690193","https://openalex.org/W3003058300","https://openalex.org/W3013324370","https://openalex.org/W3016092372","https://openalex.org/W3029644242","https://openalex.org/W3044807317","https://openalex.org/W3045884835","https://openalex.org/W3080362910","https://openalex.org/W3084241168","https://openalex.org/W3097206347","https://openalex.org/W3119057232","https://openalex.org/W3162721188","https://openalex.org/W3168119119","https://openalex.org/W4200615353","https://openalex.org/W4205355037","https://openalex.org/W4292616360","https://openalex.org/W4304943281","https://openalex.org/W4361215760","https://openalex.org/W4386216146","https://openalex.org/W4391067047","https://openalex.org/W4391277955","https://openalex.org/W4393390344","https://openalex.org/W4396857460","https://openalex.org/W4399292897","https://openalex.org/W4399505243","https://openalex.org/W4404455943","https://openalex.org/W4404937304","https://openalex.org/W4405249279","https://openalex.org/W4407844690","https://openalex.org/W4408123743","https://openalex.org/W4410209104","https://openalex.org/W4411436154","https://openalex.org/W4411647028","https://openalex.org/W4411709767","https://openalex.org/W4414646584","https://openalex.org/W4416143454","https://openalex.org/W4417068360","https://openalex.org/W7097432222","https://openalex.org/W7134119110"],"related_works":["https://openalex.org/W7162772967","https://openalex.org/W4417068360","https://openalex.org/W4404937304","https://openalex.org/W4385555019","https://openalex.org/W4396546588","https://openalex.org/W4396589911","https://openalex.org/W4391067047","https://openalex.org/W4309697359","https://openalex.org/W7204480724","https://openalex.org/W4291183990"],"abstract_inverted_index":{"The":[0],"tumor":[1,77,113],"microenvironment":[2],"is":[3,41,104],"characterized":[4],"not":[5],"only":[6],"by":[7,12,80,157,236],"biochemical":[8,69],"alterations":[9],"but":[10],"also":[11,124],"profound":[13],"biophysical":[14,67,74],"abnormalities,":[15],"among":[16],"which":[17],"increased":[18],"extracellular":[19],"matrix":[20,39,60,215],"(ECM)":[21],"stiffness":[22,40,61,216],"represents":[23],"a":[24,33],"defining":[25],"hallmark":[26],"of":[27,37,49,57,76,129],"solid":[28],"malignancies.":[29],"Once":[30],"regarded":[31],"as":[32,44,139,141],"passive":[34],"structural":[35],"consequence":[36],"desmoplasia,":[38],"now":[42],"recognized":[43],"an":[45],"active,":[46],"master":[47],"regulator":[48],"anti-tumor":[50],"immunity.":[51],"This":[52],"review":[53],"synthesizes":[54],"current":[55],"understanding":[56],"how":[58,94,151],"elevated":[59],"orchestrates":[62],"immune":[63,188,231],"suppression":[64],"through":[65,171],"interconnected":[66],"and":[68,87,146,186,193,208,222,226,240],"mechanisms.":[70],"We":[71,91,123,148,195,234],"delineate":[72],"the":[73,111,126,172],"basis":[75],"stiffening":[78],"driven":[79],"enhanced":[81],"collagen":[82],"deposition,":[83],"lysyl":[84],"oxidase-mediated":[85],"crosslinking,":[86],"cancer-associated":[88],"fibroblast":[89],"activation.":[90],"systematically":[92],"examine":[93],"stiff":[95,112,152],"matrices":[96,153],"reshape":[97],"innate":[98],"immunity,":[99],"emphasizing":[100],"that":[101,132,201],"macrophage":[102],"polarization":[103],"context-dependent:":[105],"M2-like":[106],"immunosuppressive":[107,137],"phenotypes":[108],"predominate":[109],"in":[110],"stroma,":[114],"whereas":[115],"defined":[116],"biomaterial":[117],"substrates":[118],"can":[119],"prime":[120],"inflammatory":[121],"states.":[122],"cover":[125],"metabolic":[127],"reprogramming":[128],"tumor-associated":[130],"macrophages":[131],"depletes":[133],"arginine":[134],"while":[135],"secreting":[136],"ornithine,":[138],"well":[140],"altered":[142],"dendritic":[143],"cell":[144,168,183],"maturation":[145],"function.":[147],"then":[149],"discuss":[150,197],"suppress":[154],"adaptive":[155],"immunity":[156],"physically":[158],"impeding":[159],"T":[160,167,182],"lymphocyte":[161],"migration,":[162],"actively":[163],"inducing":[164],"CD8":[165],"+":[166,176],"terminal":[169],"exhaustion":[170],"recently":[173],"discovered":[174],"Piezo1/Ca\u00b2":[175],"/CaMKII/CREB/Osr2":[177],"biomechanical":[178],"checkpoint,":[179],"promoting":[180],"regulatory":[181],"(Treg)":[184],"differentiation,":[185],"upregulating":[187],"checkpoint":[189,232],"ligands":[190],"including":[191],"PD-L1":[192],"PD-L2.":[194],"further":[196],"mechanotransduction":[198],"signaling":[199],"cascades":[200],"translate":[202],"physical":[203],"cues":[204],"into":[205,247],"immunological":[206],"outcomes,":[207],"evaluate":[209],"emerging":[210],"therapeutic":[211],"strategies":[212],"to":[213],"normalize":[214],"(including":[217],"ECM-targeting":[218],"agents,":[219],"mechanosignaling":[220],"inhibitors,":[221],"mechano-optimized":[223],"cellular":[224],"therapies)":[225],"their":[227],"synergistic":[228],"combination":[229],"with":[230],"blockade.":[233],"conclude":[235],"highlighting":[237],"key":[238],"challenges":[239],"future":[241],"directions":[242],"for":[243],"translating":[244],"mechano-immunological":[245],"insights":[246],"clinical":[248],"practice.":[249]},"counts_by_year":[],"updated_date":"2026-11-11T12:16:26.678958","created_date":"2026-11-10T00:00:00"}
