{"id":"https://openalex.org/W7224801656","doi":"https://doi.org/10.3389/fimmu.2026.1996730","title":"Complement in cancer-associated fibroblasts: sources, regulation and context dependence","display_name":"Complement in cancer-associated fibroblasts: sources, regulation and context dependence","publication_year":2026,"publication_date":"2026-10-30","ids":{"openalex":"https://openalex.org/W7224801656","doi":"https://doi.org/10.3389/fimmu.2026.1996730"},"language":"en","primary_location":{"id":"doi:10.3389/fimmu.2026.1996730","doi":"https://doi.org/10.3389/fimmu.2026.1996730","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fimmu.2026.1996730","pdf_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1996730/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","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","indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1996730/pdf","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5016117560","display_name":"Kaiqi Lei","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I91136226","display_name":"University of Sheffield","ror":"https://ror.org/05krs5044","country_code":"GB","type":"education","lineage":["https://openalex.org/I91136226"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Kaiqi Lei","raw_affiliation_strings":["School of Biosciences, University of Sheffield"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"School of Biosciences, University of Sheffield","institution_ids":["https://openalex.org/I91136226"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5016117560"],"corresponding_institution_ids":["https://openalex.org/I91136226"],"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":0.7871507,"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/T10993","display_name":"Complement system in diseases","score":0.8848000168800354,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10993","display_name":"Complement system in diseases","score":0.8848000168800354,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10231","display_name":"Pancreatic and Hepatic Oncology Research","score":0.021400000900030136,"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/T11313","display_name":"Immune cells in cancer","score":0.017400000244379044,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/complement-system","display_name":"complement system","score":0.9449999928474426},{"id":"https://openalex.org/keywords/cancer-associated-fibroblasts","display_name":"cancer-associated fibroblasts","score":0.9990000128746033},{"id":"https://openalex.org/keywords/inflammatory-cafs","display_name":"inflammatory CAFs","score":0.7400000095367432},{"id":"https://openalex.org/keywords/complement-proteins","display_name":"complement proteins","score":0.4320000112056732},{"id":"https://openalex.org/keywords/fibroblast-secretome","display_name":"fibroblast secretome","score":0.7020000219345093},{"id":"https://openalex.org/keywords/tumor-microenvironment","display_name":"tumor microenvironment","score":0.7670000195503235},{"id":"https://openalex.org/keywords/tumor-progression","display_name":"tumor progression","score":0.5899999737739563},{"id":"https://openalex.org/keywords/chronic-inflammation","display_name":"chronic inflammation","score":0.5609999895095825},{"id":"https://openalex.org/keywords/pancreatic-cancer","display_name":"pancreatic cancer","score":0.5590000152587891},{"id":"https://openalex.org/keywords/breast-cancer","display_name":"breast cancer","score":0.9649999737739563},{"id":"https://openalex.org/keywords/uveal-melanoma","display_name":"uveal melanoma","score":0.7760000228881836},{"id":"https://openalex.org/keywords/head-and-neck-cancer","display_name":"head and neck cancer","score":0.878000020980835},{"id":"https://openalex.org/keywords/esophageal-cancer","display_name":"esophageal cancer","score":0.8859999775886536}],"concepts":[{"id":"https://openalex.org/C162317418","wikidata":"https://www.wikidata.org/wiki/Q252857","display_name":"Transcriptome","level":4,"score":0.6653000116348267},{"id":"https://openalex.org/C112313634","wikidata":"https://www.wikidata.org/wiki/Q7886648","display_name":"Complement (music)","level":5,"score":0.6328999996185303},{"id":"https://openalex.org/C111684460","wikidata":"https://www.wikidata.org/wiki/Q334848","display_name":"Complement system","level":3,"score":0.5633999705314636},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4668000042438507},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.40619999170303345},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.40059998631477356},{"id":"https://openalex.org/C2779343474","wikidata":"https://www.wikidata.org/wiki/Q3109175","display_name":"Context (archaeology)","level":2,"score":0.38589999079704285},{"id":"https://openalex.org/C18431079","wikidata":"https://www.wikidata.org/wiki/Q1502169","display_name":"Gene expression profiling","level":4,"score":0.3720000088214874},{"id":"https://openalex.org/C138873322","wikidata":"https://www.wikidata.org/wiki/Q83130456","display_name":"Complement control protein","level":5,"score":0.3718000054359436},{"id":"https://openalex.org/C2776914184","wikidata":"https://www.wikidata.org/wiki/Q101991","display_name":"Inflammation","level":2,"score":0.36579999327659607},{"id":"https://openalex.org/C49039625","wikidata":"https://www.wikidata.org/wiki/Q84230","display_name":"Secretion","level":2,"score":0.33649998903274536},{"id":"https://openalex.org/C191590540","wikidata":"https://www.wikidata.org/wiki/Q5969289","display_name":"iC3b","level":4,"score":0.3287000060081482},{"id":"https://openalex.org/C2777658100","wikidata":"https://www.wikidata.org/wiki/Q180614","display_name":"Melanoma","level":2,"score":0.32339999079704285},{"id":"https://openalex.org/C184404459","wikidata":"https://www.wikidata.org/wiki/Q5009828","display_name":"CD59","level":4,"score":0.3215999901294708},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.31779998540878296},{"id":"https://openalex.org/C203473731","wikidata":"https://www.wikidata.org/wiki/Q14874317","display_name":"Complement component 3","level":5,"score":0.3041999936103821},{"id":"https://openalex.org/C189446657","wikidata":"https://www.wikidata.org/wiki/Q4736500","display_name":"Alternative complement pathway","level":4,"score":0.2955999970436096},{"id":"https://openalex.org/C127716648","wikidata":"https://www.wikidata.org/wiki/Q104053","display_name":"Phenotype","level":3,"score":0.29499998688697815},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.28949999809265137},{"id":"https://openalex.org/C165864922","wikidata":"https://www.wikidata.org/wiki/Q411391","display_name":"Regulation of gene expression","level":3,"score":0.28630000352859497},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.2773999869823456},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.27489998936653137},{"id":"https://openalex.org/C171279029","wikidata":"https://www.wikidata.org/wiki/Q5128320","display_name":"Classical complement pathway","level":4,"score":0.26980000734329224},{"id":"https://openalex.org/C179369057","wikidata":"https://www.wikidata.org/wiki/Q20970075","display_name":"Complement factor I","level":4,"score":0.26899999380111694},{"id":"https://openalex.org/C2778442404","wikidata":"https://www.wikidata.org/wiki/Q55505","display_name":"Xenotransplantation","level":3,"score":0.2687999904155731},{"id":"https://openalex.org/C127561419","wikidata":"https://www.wikidata.org/wiki/Q224527","display_name":"Downregulation and upregulation","level":3,"score":0.2687000036239624},{"id":"https://openalex.org/C2910311954","wikidata":"https://www.wikidata.org/wiki/Q21116899","display_name":"Complement C1q","level":4,"score":0.2687000036239624},{"id":"https://openalex.org/C136015124","wikidata":"https://www.wikidata.org/wiki/Q13566093","display_name":"Complement component 2","level":5,"score":0.25519999861717224}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.3389/fimmu.2026.1996730","doi":"https://doi.org/10.3389/fimmu.2026.1996730","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fimmu.2026.1996730","pdf_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1996730/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","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"},{"id":"pmh:oai:doaj.org/article:1ce5df32aa7846a7abbcf992038e1750","doi":null,"is_oa":false,"landing_page_url":"https://doaj.org/article/1ce5df32aa7846a7abbcf992038e1750","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Frontiers in Immunology, Vol 17 (2026)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.3389/fimmu.2026.1996730","doi":"https://doi.org/10.3389/fimmu.2026.1996730","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fimmu.2026.1996730","pdf_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1996730/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","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":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.9537000060081482}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320320342","display_name":"University of Sheffield","ror":"https://ror.org/05krs5044"}],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7224801656.pdf","grobid_xml":"https://content.openalex.org/works/W7224801656.grobid-xml"},"referenced_works_count":52,"referenced_works":["https://openalex.org/W7411795","https://openalex.org/W1483191540","https://openalex.org/W1498374831","https://openalex.org/W1963657283","https://openalex.org/W1967532362","https://openalex.org/W1987200598","https://openalex.org/W1995545538","https://openalex.org/W2037699401","https://openalex.org/W2048381031","https://openalex.org/W2054584654","https://openalex.org/W2064595835","https://openalex.org/W2098504065","https://openalex.org/W2117349053","https://openalex.org/W2169455496","https://openalex.org/W2590390825","https://openalex.org/W2591992124","https://openalex.org/W2611780568","https://openalex.org/W2894350935","https://openalex.org/W2898435366","https://openalex.org/W2942898054","https://openalex.org/W2951222857","https://openalex.org/W3026654828","https://openalex.org/W3043476556","https://openalex.org/W3128249589","https://openalex.org/W3147787140","https://openalex.org/W3157044496","https://openalex.org/W3163348136","https://openalex.org/W3175990841","https://openalex.org/W4229456682","https://openalex.org/W4299286463","https://openalex.org/W4322631830","https://openalex.org/W4381715545","https://openalex.org/W4382985816","https://openalex.org/W4386877758","https://openalex.org/W4389899950","https://openalex.org/W4390276657","https://openalex.org/W4392892505","https://openalex.org/W4400576293","https://openalex.org/W4402639753","https://openalex.org/W4404164420","https://openalex.org/W4404836519","https://openalex.org/W4405642321","https://openalex.org/W4406861095","https://openalex.org/W4407508530","https://openalex.org/W4408116821","https://openalex.org/W4411604723","https://openalex.org/W4416897326","https://openalex.org/W7123830169","https://openalex.org/W7130683238","https://openalex.org/W7133950411","https://openalex.org/W7134278613","https://openalex.org/W7155098304"],"related_works":["https://openalex.org/W2139788242","https://openalex.org/W2888916986","https://openalex.org/W3086823661","https://openalex.org/W6906648020","https://openalex.org/W3134165232","https://openalex.org/W7123830169","https://openalex.org/W3198094729","https://openalex.org/W1179357147","https://openalex.org/W7223679598","https://openalex.org/W4311957070"],"abstract_inverted_index":{"Complement":[0],"genes":[1],"recur":[2],"in":[3,45,56,137],"the":[4,67,73,80,90,94,183,201,207],"transcriptomes":[5],"of":[6,35,72],"cancer-associated":[7],"fibroblasts":[8,111,141],"(CAFs)":[9],"and":[10,20,69,78,126,139,148,161,197,209,212],"have":[11],"been":[12],"independently":[13],"reproduced":[14],"across":[15],"pancreatic,":[16],"breast,":[17],"oesophageal,":[18],"head-and-neck":[19],"uveal":[21],"melanoma":[22],"tumours.":[23],"This":[24],"review":[25],"argues":[26],"that":[27,38,142,182,220],"complement":[28,54,130,176,204,218],"is":[29,61,87,98,116,181,186],"a":[30,117,122,133,166,169,174,216],"real,":[31],"perturbable":[32],"functional":[33,64],"dimension":[34],"fibroblasts,":[36,203],"but":[37,191],"four":[39,224],"questions":[40,225],"central":[41,179],"to":[42,63,100],"interpreting":[43],"it":[44],"cancer":[46],"remain":[47],"unresolved:":[48],"which":[49],"cell":[50],"contributes":[51],"how":[52],"much":[53],"protein":[55,208],"intact":[57],"tissue;":[58],"whether":[59,66,79],"production":[60],"coupled":[62],"self-protection;":[65],"proximal":[68],"terminal":[70],"ends":[71],"cascade":[74],"are":[75],"differentially":[76],"regulated;":[77],"malignant":[81,167,196],"secretome,":[82],"rather":[83,120],"than":[84,121],"generic":[85],"stress,":[86],"what":[88],"induces":[89],"phenotype.":[91],"Across":[92],"studies":[93],"same":[95,202],"recurrent":[96],"signature":[97],"assigned":[99],"at":[101,206,226],"least":[102],"seven":[103],"different":[104],"CAF":[105],"state":[106],"labels,":[107],"so":[108],"equating":[109],"complement-positive":[110],"with":[112,144,168,215],"inflammatory":[113],"CAFs":[114],"(iCAFs)":[115],"naming":[118],"convention":[119],"validated":[123],"attribution.":[124],"Trajectory":[125],"atlas":[127,190],"evidence":[128,150],"suggest":[129],"may":[131],"be":[132],"feature":[134],"already":[135],"present":[136],"normal":[138],"early":[140],"declines":[143],"progression;":[145],"direct":[146],"induction":[147],"perturbation":[149,214],"comes":[151],"mainly":[152],"from":[153],"therapeutic":[154],"injury,":[155],"chronic":[156],"inflammation":[157],"or":[158],"already-established":[159],"CAFs;":[160],"no":[162],"study":[163],"yet":[164],"pairs":[165],"matched":[170],"non-malignant":[171,198],"secretome":[172],"under":[173],"multi-component":[175],"readout.":[177],"The":[178],"message":[180],"next":[184],"step":[185],"not":[187],"another":[188],"transcriptomic":[189],"one":[192],"defined":[193],"experiment":[194],"paired":[195],"inputs":[199],"on":[200],"quantified":[205],"secretion":[210],"level,":[211],"fibroblast-specific":[213],"tissue":[217],"readout,":[219],"would":[221],"address":[222],"all":[223],"once.":[227]},"counts_by_year":[],"updated_date":"2026-11-02T09:45:03.842371","created_date":"2026-10-31T00:00:00"}