{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T08:52:10Z","timestamp":1789548730280,"version":"build-2803163510"},"reference-count":105,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001502","name":"Department of Atomic Energy, Government of India","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001502","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Melanoma, a highly aggressive skin cancer, ranks fifth among Caucasians and has a high mutation rate. Despite advances in immunotherapy, over 40% of patients face immune\u2010related side effects. Neuropilin\u20101 (NRP1), which is overexpressed in various cancers, enhances the function of Treg cells and promotes tumour growth, thereby contributing to poor patient outcomes. This study investigated the effects of NRP1 inhibition in B16\u2010F10 melanoma, with a focus on its impact on immune responses regulated by peripheral T regulatory cells (Tregs). NRP1 was found to be overexpressed in the majority of cancer patient samples and cancer cell lines, including melanoma, as indicated by cBioPortal and the human protein atlas database analysis, establishing a positive correlation between NRP1 and various cancers. mRNA studies revealed elevated NRP1 expression in tumorigenic B16\u2010F10 cells compared with non\u2010tumorigenic NIH\u20103T3 cells. Inhibition of NRP1 induced apoptosis in B16\u2010F10 cells without affecting NIH\u20103T3 cells. It also reversed the immunosuppression caused by B16\u2010F10\u2010cell culture supernatant (B16\u2010F10\u2010CS), reducing the Treg population (NRP1, NKG2A, and FOXP3), Treg suppressive activity and the secretion of immunomodulatory cytokines (IL\u201010 and IL\u201017A) while increasing T cell proliferation and the secretion of effector cytokines (TNF, IFN\u2010\u03b3, IL\u20106, and IL\u20102). Additionally, NRP1 inhibition suppressed the STAT, ERK MAPK, and Smad2\/3 pathways and activated the PI3K\/AKT pathway in Tregs cultured in B16\u2010F10\u2010CS in\u00a0vitro. In tumour\u2010bearing mice, NRP1 inhibition decreased Treg and Th2 population marker expression and enhanced T cell proliferation and Th1 population marker expression in peripheral Tregs. It also reduced lung metastasis, decreased tumour size, and improved survival. These findings suggest that targeting NRP1 could slow melanoma progression and reduce peripheral Treg\u2010mediated immunosuppression, making it a promising approach for future cancer immunotherapies, especially in combination with other treatments.<\/jats:p>","DOI":"10.1111\/imm.70072","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T06:17:31Z","timestamp":1764310651000},"page":"613-637","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Targeting Neuropilin\u20101 to Enhance Immunotherapy in Melanoma: Reducing Peripheral Treg\u2010Mediated Immunosuppression and Tumour Progression"],"prefix":"10.1111","volume":"177","author":[{"given":"Somlata","family":"Khamaru","sequence":"first","affiliation":[{"name":"School of Biological Sciences National Institute of Science Education and Research  Bhubaneswar Odisha India"},{"name":"Homi Bhabha National Institute, Training School Complex  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kshyama Subhadarsini","family":"Tung","sequence":"additional","affiliation":[{"name":"School of Biological Sciences National Institute of Science Education and Research  Bhubaneswar Odisha India"},{"name":"Homi Bhabha National Institute, Training School Complex  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2596-8451","authenticated-orcid":false,"given":"Subhasis","family":"Chattopadhyay","sequence":"additional","affiliation":[{"name":"School of Biological Sciences National Institute of Science Education and Research  Bhubaneswar Odisha India"},{"name":"Homi Bhabha National Institute, Training School Complex  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"e_1_2_14_2_1","first-page":"139","article-title":"Epidemiology of Melanoma","volume":"6","author":"Matthews N. H.","year":"2017","journal-title":"Progress in Clinical Cancer"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2012.04.018"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262\u2010005\u20100699\u20109"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.2.984"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm730"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29930-0"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01228"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13081850"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101621"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)01206-X"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2015.03.004"},{"key":"e_1_2_14_13_1","first-page":"1","article-title":"Cell Death\u2010Based Treatments of Melanoma: Conventional Treatments and New Therapeutic Strategies","volume":"9","author":"Mattia G.","year":"2024","journal-title":"Cell Death & Disease"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0306-5"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02453"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12520"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-018-0313-5"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115142"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.70.2.219"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200322919"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.960852"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2023.07.002"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2014.04.002"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010024\u201005104\u2010y"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01141-1"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23052847"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-000967"},{"key":"e_1_2_14_28_1","volume-title":"Structural and Functional Relation of Neuropilins","author":"Nakamura F.","year":"2013"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.665634"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12428"},{"key":"e_1_2_14_31_1","doi-asserted-by":"crossref","unstructured":"O.Mccarty M.Postow P. M.Lacal andG.Graziani \u201cMini Review Neuropilin\u20101 as Therapeutic Target for Malignant Melanoma \u201d5(2015):125 https:\/\/www.frontiersin.org.","DOI":"10.3389\/fonc.2015.00125"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000001200"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05696-1"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00662"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12123582"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15204922"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000320"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-19-0143"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.56123"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2022.175290"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-019-0105-2"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116766"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2015.00125"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2011.01024.x"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7199"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.1089\/cbr.2018.2672"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-012-1258-3"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2404916121"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.21037\/aob-20-53"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.1158\/2767-9764.CRC-22-0250"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im2001s39"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-01097-8"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.507"},{"key":"e_1_2_14_54_1","doi-asserted-by":"publisher","DOI":"10.1101\/2023.11.07.564946v2"},{"key":"e_1_2_14_55_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-3687"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1093"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2007.03.053"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.4049\/immunohorizons.2400046"},{"key":"e_1_2_14_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.2011.01266.x"},{"key":"e_1_2_14_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33859"},{"key":"e_1_2_14_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2015.12.009"},{"key":"e_1_2_14_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.005"},{"key":"e_1_2_14_63_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102011\u201001\u2010329268"},{"key":"e_1_2_14_64_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.900139"},{"key":"e_1_2_14_65_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.790787"},{"key":"e_1_2_14_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/neup.12966"},{"key":"e_1_2_14_67_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2024.14247\/abstract"},{"key":"e_1_2_14_68_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.685980"},{"key":"e_1_2_14_69_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.715901"},{"key":"e_1_2_14_70_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1055805"},{"key":"e_1_2_14_71_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00882"},{"key":"e_1_2_14_72_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_14_73_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abf8495"},{"key":"e_1_2_14_74_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-05104-y"},{"key":"e_1_2_14_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107297"},{"key":"e_1_2_14_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2024.107022"},{"key":"e_1_2_14_77_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v17.i15.2019"},{"key":"e_1_2_14_78_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2011.01018.x"},{"key":"e_1_2_14_79_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI99257"},{"key":"e_1_2_14_80_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111497"},{"key":"e_1_2_14_81_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964\u2010024\u201001505\u20100"},{"key":"e_1_2_14_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14649"},{"key":"e_1_2_14_83_1","doi-asserted-by":"publisher","DOI":"10.4110\/in.2017.17.5.276"},{"key":"e_1_2_14_84_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202350730"},{"key":"e_1_2_14_85_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-013-1500-0"},{"key":"e_1_2_14_86_1","doi-asserted-by":"publisher","DOI":"10.1159\/000067596"},{"key":"e_1_2_14_87_1","doi-asserted-by":"publisher","DOI":"10.1177\/20503121211069012"},{"key":"e_1_2_14_88_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838913"},{"key":"e_1_2_14_89_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M910149199"},{"key":"e_1_2_14_90_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S256708"},{"key":"e_1_2_14_91_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.9838.1"},{"key":"e_1_2_14_92_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.11.7593"},{"key":"e_1_2_14_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2018.06.030"},{"key":"e_1_2_14_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-01036-7"},{"key":"e_1_2_14_95_1","doi-asserted-by":"publisher","DOI":"10.1080\/09553002.2020.1793015"},{"key":"e_1_2_14_96_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01526"},{"key":"e_1_2_14_97_1","doi-asserted-by":"publisher","DOI":"10.62347\/RLVZ6860"},{"key":"e_1_2_14_98_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600811"},{"key":"e_1_2_14_99_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756\u20109966\u201029\u201022"},{"key":"e_1_2_14_100_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines7040149"},{"key":"e_1_2_14_101_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2010.20"},{"key":"e_1_2_14_102_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57456"},{"key":"e_1_2_14_103_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adk2693"},{"key":"e_1_2_14_104_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104353"},{"key":"e_1_2_14_105_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.958620"},{"key":"e_1_2_14_106_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6877"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.70072","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/imm.70072","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.70072","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:28:33Z","timestamp":1771028913000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.70072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,27]]},"references-count":105,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1111\/imm.70072"],"URL":"https:\/\/doi.org\/10.1111\/imm.70072","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,27]]},"assertion":[{"value":"2025-03-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}