{"id":"https://openalex.org/W7005539475","doi":null,"title":"Reprogramming the Tumor Microenvironment to Increase the Efficacy of Treatment in Therapy-Resistant Patients with Pancreatic Ductal Adenocarcinoma","display_name":"Reprogramming the Tumor Microenvironment to Increase the Efficacy of Treatment in Therapy-Resistant Patients with Pancreatic Ductal Adenocarcinoma","publication_year":2024,"publication_date":"2024-01-01","ids":{"openalex":"https://openalex.org/W7005539475"},"language":"en","primary_location":{"id":"pmh:oai:repository.arizona.edu:10150/675274","doi":null,"is_oa":false,"landing_page_url":"https://repository.arizona.edu/bitstream/handle/10150/675274/azu_etd_21668_sip1_m.pdf?sequence=1&isAllowed=n","pdf_url":null,"source":{"id":"https://openalex.org/S4306400271","display_name":"UA Campus Repository (The University of Arizona)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I138006243","host_organization_name":"University of Arizona","host_organization_lineage":["https://openalex.org/I138006243"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Electronic Dissertation"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":null,"display_name":"Adhikary, Pritha","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Adhikary, Pritha","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":null,"display_name":"Adhikary, Pritha","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Adhikary, Pritha","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":true,"primary_topic":{"id":"https://openalex.org/T10231","display_name":"Pancreatic and Hepatic Oncology Research","score":0.9907000064849854,"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"}},"topics":[{"id":"https://openalex.org/T10231","display_name":"Pancreatic and Hepatic Oncology Research","score":0.9907000064849854,"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/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.00800000037997961,"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/T12505","display_name":"Peptidase Inhibition and Analysis","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/1303","display_name":"Biochemistry"},"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/pancreatic-ductal-adenocarcinoma","display_name":"pancreatic ductal adenocarcinoma","score":1.0},{"id":"https://openalex.org/keywords/tumor-microenvironment","display_name":"tumor microenvironment","score":0.8949999809265137},{"id":"https://openalex.org/keywords/cabozantinib","display_name":"cabozantinib","score":0.8899999856948853},{"id":"https://openalex.org/keywords/myeloid-derived-suppressor-cells","display_name":"myeloid-derived suppressor cells","score":0.8939999938011169},{"id":"https://openalex.org/keywords/cancer-associated-fibroblasts","display_name":"cancer-associated fibroblasts","score":0.8270000219345093},{"id":"https://openalex.org/keywords/immunotherapy-resistance","display_name":"immunotherapy resistance","score":0.6679999828338623},{"id":"https://openalex.org/keywords/pd-1-pd-l1-inhibitors","display_name":"PD-1/PD-L1 inhibitors","score":0.9449999928474426},{"id":"https://openalex.org/keywords/pembrolizumab","display_name":"pembrolizumab","score":0.9729999899864197},{"id":"https://openalex.org/keywords/atezolizumab","display_name":"atezolizumab","score":0.996999979019165},{"id":"https://openalex.org/keywords/spatial-transcriptomics","display_name":"spatial transcriptomics","score":0.47600001096725464},{"id":"https://openalex.org/keywords/organoids","display_name":"organoids","score":0.7519999742507935},{"id":"https://openalex.org/keywords/tumor-heterogeneity","display_name":"tumor heterogeneity","score":0.5669999718666077}],"concepts":[{"id":"https://openalex.org/C2776107976","wikidata":"https://www.wikidata.org/wiki/Q1786433","display_name":"Tumor microenvironment","level":3,"score":0.7843000292778015},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.6564000248908997},{"id":"https://openalex.org/C2780210213","wikidata":"https://www.wikidata.org/wiki/Q212961","display_name":"Pancreatic cancer","level":3,"score":0.6518999934196472},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.6306999921798706},{"id":"https://openalex.org/C2781064419","wikidata":"https://www.wikidata.org/wiki/Q795057","display_name":"Cabozantinib","level":3,"score":0.5809000134468079},{"id":"https://openalex.org/C2777701055","wikidata":"https://www.wikidata.org/wiki/Q1427096","display_name":"Immunotherapy","level":3,"score":0.5171999931335449},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.5151000022888184},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.46639999747276306},{"id":"https://openalex.org/C16930146","wikidata":"https://www.wikidata.org/wiki/Q4381253","display_name":"Stromal cell","level":2,"score":0.4587000012397766},{"id":"https://openalex.org/C96232424","wikidata":"https://www.wikidata.org/wiki/Q4118072","display_name":"Cancer cell","level":3,"score":0.45260000228881836},{"id":"https://openalex.org/C2909706936","wikidata":"https://www.wikidata.org/wiki/Q42417562","display_name":"Cancer-Associated Fibroblasts","level":4,"score":0.44670000672340393},{"id":"https://openalex.org/C52124034","wikidata":"https://www.wikidata.org/wiki/Q557179","display_name":"Stroma","level":3,"score":0.4401000142097473},{"id":"https://openalex.org/C2908647359","wikidata":"https://www.wikidata.org/wiki/Q2625603","display_name":"Population","level":2,"score":0.42309999465942383},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.3684999942779541},{"id":"https://openalex.org/C77255625","wikidata":"https://www.wikidata.org/wiki/Q402093","display_name":"Reprogramming","level":3,"score":0.3668000102043152},{"id":"https://openalex.org/C55721878","wikidata":"https://www.wikidata.org/wiki/Q15220362","display_name":"Myeloid-derived Suppressor Cell","level":4,"score":0.32519999146461487},{"id":"https://openalex.org/C535046627","wikidata":"https://www.wikidata.org/wiki/Q30612","display_name":"Clinical trial","level":2,"score":0.30889999866485596},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.3000999987125397},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.2976999878883362},{"id":"https://openalex.org/C2780674031","wikidata":"https://www.wikidata.org/wiki/Q2012719","display_name":"Cancer immunotherapy","level":4,"score":0.29319998621940613},{"id":"https://openalex.org/C2781182431","wikidata":"https://www.wikidata.org/wiki/Q356033","display_name":"Adenocarcinoma","level":3,"score":0.29269999265670776},{"id":"https://openalex.org/C2778087573","wikidata":"https://www.wikidata.org/wiki/Q418369","display_name":"Erlotinib","level":4,"score":0.28790000081062317},{"id":"https://openalex.org/C55427017","wikidata":"https://www.wikidata.org/wiki/Q1638475","display_name":"Cancer stem cell","level":3,"score":0.2777000069618225},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.27230000495910645},{"id":"https://openalex.org/C61238886","wikidata":"https://www.wikidata.org/wiki/Q5121689","display_name":"Circulating tumor cell","level":4,"score":0.27160000801086426},{"id":"https://openalex.org/C2780851360","wikidata":"https://www.wikidata.org/wiki/Q21686041","display_name":"Immune checkpoint","level":4,"score":0.26969999074935913},{"id":"https://openalex.org/C2780258809","wikidata":"https://www.wikidata.org/wiki/Q414143","display_name":"Gemcitabine","level":3,"score":0.2531000077724457},{"id":"https://openalex.org/C2779256057","wikidata":"https://www.wikidata.org/wiki/Q16909647","display_name":"Tumor progression","level":3,"score":0.24289999902248383},{"id":"https://openalex.org/C2776694085","wikidata":"https://www.wikidata.org/wiki/Q974135","display_name":"Chemotherapy","level":2,"score":0.24060000479221344},{"id":"https://openalex.org/C179185449","wikidata":"https://www.wikidata.org/wiki/Q219699","display_name":"Suppressor","level":3,"score":0.23980000615119934},{"id":"https://openalex.org/C2780394083","wikidata":"https://www.wikidata.org/wiki/Q539568","display_name":"Angiogenesis","level":2,"score":0.23330000042915344},{"id":"https://openalex.org/C2779013556","wikidata":"https://www.wikidata.org/wiki/Q181876","display_name":"Metastasis","level":3,"score":0.23260000348091125},{"id":"https://openalex.org/C2776283816","wikidata":"https://www.wikidata.org/wiki/Q332823","display_name":"Survival rate","level":2,"score":0.23240000009536743},{"id":"https://openalex.org/C2781230642","wikidata":"https://www.wikidata.org/wiki/Q492646","display_name":"Targeted therapy","level":3,"score":0.2222999930381775},{"id":"https://openalex.org/C76419328","wikidata":"https://www.wikidata.org/wiki/Q74419","display_name":"Epithelial\u2013mesenchymal transition","level":4,"score":0.22220000624656677},{"id":"https://openalex.org/C2778764654","wikidata":"https://www.wikidata.org/wiki/Q9618","display_name":"Pancreas","level":2,"score":0.22220000624656677},{"id":"https://openalex.org/C2779282312","wikidata":"https://www.wikidata.org/wiki/Q1956561","display_name":"Myeloid","level":2,"score":0.2176000028848648},{"id":"https://openalex.org/C63363279","wikidata":"https://www.wikidata.org/wiki/Q5133848","display_name":"Clinical significance","level":2,"score":0.2150000035762787},{"id":"https://openalex.org/C526805850","wikidata":"https://www.wikidata.org/wiki/Q188874","display_name":"Colorectal cancer","level":3,"score":0.21439999341964722},{"id":"https://openalex.org/C2992026798","wikidata":"https://www.wikidata.org/wiki/Q212961","display_name":"Pancreatic ductal adenocarcinoma","level":4,"score":0.21289999783039093}],"mesh":[],"locations_count":1,"locations":[{"id":"pmh:oai:repository.arizona.edu:10150/675274","doi":null,"is_oa":false,"landing_page_url":"https://repository.arizona.edu/bitstream/handle/10150/675274/azu_etd_21668_sip1_m.pdf?sequence=1&isAllowed=n","pdf_url":null,"source":{"id":"https://openalex.org/S4306400271","display_name":"UA Campus Repository (The University of Arizona)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I138006243","host_organization_name":"University of Arizona","host_organization_lineage":["https://openalex.org/I138006243"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Electronic Dissertation"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":1.0}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4393073437","https://openalex.org/W7154779170","https://openalex.org/W3080878176","https://openalex.org/W4308772998","https://openalex.org/W2771829602","https://openalex.org/W4399177115","https://openalex.org/W4402187477","https://openalex.org/W4393096342","https://openalex.org/W7160300692","https://openalex.org/W7126336767"],"abstract_inverted_index":{"SIGNIFICANCE":[0],"OF":[1],"THESE":[2],"STUDIES:":[3],"Pancreatic":[4],"Ductal":[5],"Adenocarcinoma":[6],"(PDAC)":[7],"is":[8,45,173],"one":[9],"of":[10,14,30,41,52,56,73,143,163,179,189,237,259,266,275,286,293,303,322,328,336,382,393,402,429,476,520,556],"the":[11,21,48,71,108,111,126,141,152,177,186,194,207,217,243,251,257,272,276,300,319,326,334,340,377,380,389,400,411,418,433,459,469,495,504,554,557,564,568],"leading":[12],"causes":[13],"cancer":[15,57,63,77,85,114,165],"deaths":[16],"(51,750":[17],"in":[18,20,87,161,198,206,221,279,324,362,395,494,503,530,559],"2024)":[19],"United":[22],"States":[23],"and":[24,37,76,80,113,121,166,181,212,229,290,308,313,330,338,346,367,391,423,439,455,463,473,500,513,527],"has":[25],"a":[26,53,123,158,284,349,491,501,546],"5-year":[27],"survival":[28,169],"rate":[29,40],"only":[31,106],"12.8%":[32],"(2014-2020).":[33],"The":[34,154,534],"poor":[35],"prognosis":[36],"high":[38],"mortality":[39],"patients":[42,86,97,363,446],"with":[43,364,397,453,511,539,567],"PDAC":[44,96,134,199,208,267,277,310,405,477,550],"attributed":[46],"to":[47,65,100,130,175,184,215,241,255,270,281,342,359,410,543],"tumor":[49,209,252,351,496],"stroma":[50],"consisting":[51],"heterogeneous":[54,155],"population":[55,355,499],"associated":[58],"fibroblasts":[59],"(CAFs)":[60],"that":[61,139,201,356,563],"allow":[62],"cells":[64,75,115,120,248,529,542],"evade":[66],"immune":[67,128,521,541],"surveillance":[68],"by":[69,146,204,332],"promoting":[70],"infiltration":[72],"immunosuppressive":[74,137,244],"cell":[78,196,354,465,522],"proliferation":[79],"metastasis.":[81],"Even":[82],"though":[83],"certain":[84],"clinical":[88,569],"trials":[89],"have":[90,98],"shown":[91],"response":[92,280],"towards":[93],"PD-1/PD-L1":[94,104],"inhibitors,":[95],"failed":[99],"show":[101,490],"any":[102,118],"improvement.":[103],"inhibitors":[105],"block":[107],"interaction":[109],"between":[110],"T-cells":[112],"without":[116],"targeting":[117],"specific":[119],"as":[122,525,545],"result":[124],"allows":[125],"patient\u2019s":[127],"system":[129],"respond":[131],"against":[132],"cancer.":[133],"tumors":[135],"display":[136],"mechanisms":[138],"decrease":[140,493],"efficacy":[142,178,258,327,392],"T-cell":[144],"function":[145],"preventing":[147],"it":[148,172],"from":[149,417,432],"infiltrating/proliferating":[150],"within":[151,250,306],"TME.":[153],"TME":[156,200,278,335],"plays":[157],"critical":[159],"role":[160],"progression":[162],"pancreatic":[164,487],"its":[167],"low":[168],"outcome.":[170],"Therefore,":[171],"important":[174],"improve":[176],"immunotherapy":[180],"drug":[182],"targetability":[183],"increase":[185,256],"anti-tumor":[187,344],"effect":[188],"T-cells.":[190],"Our":[191,373],"studies":[192,239,375],"identified":[193,318,348],"modulated":[195],"types":[197],"are":[202],"targeted":[203],"cabozantinib":[205,323,398,454,512],"microenvironment":[210,253],"(TME)":[211,254],"allowed":[213],"us":[214],"explore":[216],"therapeutic":[218,320],"treatment":[219,401,509,532,558],"responses":[220],"immune-resistant":[222],"patients.":[223,488,551],"OBJECTIVE":[224],"AND":[225],"MAJOR":[226],"FINDINGS:":[227],"Objective":[228,235,366],"Major":[230,368],"Finding":[231],"1":[232,236],"(Chapter":[233,371],"3):":[234],"these":[238,445],"was":[240,268],"target":[242],"myeloid":[245],"derived":[246],"suppressor":[247],"(MDSC)":[249],"immunotherapy.":[260],"An":[261],"orthotopically":[262],"transplanted":[263],"mouse":[264],"model":[265,548],"used":[269],"identify":[271],"multitargeted":[273],"reprogramming":[274],"cabozantinib.":[282],"Using":[283,458],"combination":[285,396],"high\u2010plex":[287],"spatial":[288],"profiling":[289],"organoid":[291],"technologies":[292],"matched":[294],"patient":[295,415,430],"biospecimens":[296],"we":[297,413,467,561],"1)":[298],"assessed":[299],"biological":[301],"implications":[302],"heterogeneity":[304,484],"quantitatively":[305],"small":[307],"limited":[309],"core":[311],"biopsies":[312],"resected":[314],"surgical":[315],"tissues,":[316],"2)":[317],"benefit":[321],"increasing":[325],"pembrolizumab":[329],"atezolizumab":[331,394,456],"depleting":[333],"MDSCs":[337],"reprograming":[339],"CAFs":[341],"an":[343,383,518],"phenotype,":[345],"3)":[347],"potential":[350],"CD44v9":[352],"expressing":[353],"may":[357],"attribute":[358],"residual":[360],"disease":[361],"PDAC.":[365],"Findings":[369],"2":[370],"4):":[372],"preclinical":[374],"were":[376,442,447,537],"foundation":[378],"for":[379,399,449,549],"development":[381],"ongoing":[384],"Phase":[385],"II":[386],"Trial":[387],"evaluating":[388],"safety":[390],"metastatic,":[403],"refractory":[404],"(ClinicalTrials.gov":[406],"ID":[407],"NCT04820179).":[408],"Prior":[409],"treatment,":[412],"collected":[414],"tissues":[416],"metastatic":[419,435,486],"site,":[420,436],"FFPE":[421,437],"samples":[422,438,441],"blood":[424,440],"samples.":[425],"A":[426],"subsequent":[427],"collection":[428],"tissue":[431],"same":[434],"done":[443],"after":[444,507],"treated":[448],"3":[450,508],"cycles":[451,510],"(21days/cycle)":[452],"(atezo).":[457],"Nanostring":[460],"CosMx":[461,479],"SMI":[462,480],"organoid/immune":[464],"co-culture":[466],"investigated":[468],"cellular":[470],"composition,":[471],"morphology":[472],"underlying":[474],"mechanism":[475],"tumor.":[478],"revealed":[481,517],"major":[482],"intra-tumoral":[483],"among":[485],"We":[489],"significant":[492],"cells,":[497],"MDSC":[498],"change":[502],"CAF":[505],"phenotype":[506],"atezolizumab.":[514],"It":[515],"also":[516],"upregulation":[519],"populations":[523],"such":[524],"CD8+":[526],"CD4+":[528],"post":[531],"group.":[533],"patient-derived":[535],"organoids":[536],"co-cultured":[538],"autologous":[540],"serve":[544],"predictive":[547],"Upon":[552],"investigating":[553],"responsiveness":[555],"co-cultures,":[560],"found":[562],"results":[565],"correspond":[566],"data.":[570]},"counts_by_year":[],"updated_date":"2026-09-11T09:22:31.653822","created_date":"2025-10-10T00:00:00"}
