Cited 0 times in Scipus Cited Count

A Neuropilin-1 Antagonist Exerts Antitumor Immunity by Inhibiting the Suppressive Function of Intratumoral Regulatory T Cells

DC Field Value Language
dc.contributor.authorJung, K-
dc.contributor.authorKim, JA-
dc.contributor.authorKim, YJ-
dc.contributor.authorLee, HW-
dc.contributor.authorKim, CH-
dc.contributor.authorHaam, S-
dc.contributor.authorKim, YS-
dc.date.accessioned2022-11-23T07:33:03Z-
dc.date.available2022-11-23T07:33:03Z-
dc.date.issued2020-
dc.identifier.issn2326-6066-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/22895-
dc.description.abstractRegulatory T cells (Treg) are targeted for cancer immunotherapy because they suppress antitumor immunity. Although the importance of neuropilin-1 (NRP1) in the stability and function of intratumoral Tregs is well-documented, targeting of NRP1(+) Tregs for anticancer immunotherapy has not been well explored. Here, we found that an NRP1 antagonist [Fc(AAG)-TPP11], generated by fusion of the NRP1-specific binding peptide TPP11 with the C-terminus of an effector function-deficient immunoglobulin Fc(AAG) variant, inhibits intratumoral NRP1(+) Treg function and stability. Fc(AAG)-TPP11 triggered the internalization of NRP1, reducing its surface expression on Tregs and thereby inhibiting the suppressive function of Tregs. In two murine syngeneic tumor models, Fc(AAG)-TPP11 retarded tumor growth, comparable with a Treg-depleting anti-CTLA-4 antibody, without noticeable toxicity. Fc(AAG)-TPP11 inhibited NRP1-dependent Treg function, inducing unstable intratumoral Tregs, with reduced expression of Foxp3 and enhanced production of IFNgamma, which subsequently increased the functionality and frequency of intratumoral CD8(+) T cells. We also observed selective expression of NRP1 on Tregs isolated from human tumors, but not from the blood of healthy donors and patients with cancer, as well as ex vivo inhibition of intratumoral NRP1(+) Treg function by Fc(AAG)-TPP11. Our results suggest that the NRP1 antagonist Fc(AAG)-TPP11 has therapeutic potential for the inhibition of intratumoral NRP1(+) Tregs with limited unfavorable effects on peripheral Tregs.-
dc.language.isoen-
dc.subject.MESHAnimals-
dc.subject.MESHCD8-Positive T-Lymphocytes-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHColonic Neoplasms-
dc.subject.MESHFemale-
dc.subject.MESHImmunoglobulin Fc Fragments-
dc.subject.MESHImmunosuppression Therapy-
dc.subject.MESHMelanoma-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred BALB C-
dc.subject.MESHMice, Inbred C57BL-
dc.subject.MESHMice, Nude-
dc.subject.MESHNeoplasms, Experimental-
dc.subject.MESHNeuropilin-1-
dc.subject.MESHPeptide Fragments-
dc.subject.MESHSkin Neoplasms-
dc.subject.MESHT-Lymphocytes, Regulatory-
dc.titleA Neuropilin-1 Antagonist Exerts Antitumor Immunity by Inhibiting the Suppressive Function of Intratumoral Regulatory T Cells-
dc.typeArticle-
dc.identifier.pmid31554638-
dc.contributor.affiliatedAuthorJung, K-
dc.contributor.affiliatedAuthorLee, HW-
dc.contributor.affiliatedAuthorKim, CH-
dc.contributor.affiliatedAuthorHaam, S-
dc.type.localJournal Papers-
dc.identifier.doi10.1158/2326-6066.CIR-19-0143-
dc.citation.titleCancer immunology research-
dc.citation.volume8-
dc.citation.number1-
dc.citation.date2020-
dc.citation.startPage46-
dc.citation.endPage56-
dc.identifier.bibliographicCitationCancer immunology research, 8(1). : 46-56, 2020-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.identifier.eissn2326-6074-
dc.relation.journalidJ023266066-
Appears in Collections:
Journal Papers > Hospital > Clinical Trial Center
Journal Papers > School of Medicine / Graduate School of Medicine > Hematology-Oncology
Journal Papers > School of Medicine / Graduate School of Medicine > Otolaryngology
Journal Papers > School of Medicine / Graduate School of Medicine > Thoracic & Cardiovascular Surgery
Files in This Item:
There are no files associated with this item.

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse