SwePub
Sök i LIBRIS databas

  Utökad sökning

WFRF:(Björnstedt M)
 

Sökning: WFRF:(Björnstedt M) > FPR2 Shapes an Immu...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00006227naa a2200517 4500
001oai:DiVA.org:hv-21403
003SwePub
008240313s2023 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:hv:diva-214032 URI
0247 a https://doi.org/10.1158/0008-5472.can-22-29322 DOI
040 a (SwePub)hv
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a He, Feiu Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm (SWE); Department of Urology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou (CHN)4 aut
2451 0a FPR2 Shapes an Immune-Excluded Pancreatic Tumor Microenvironment and Drives T-cell Exhaustion in a Sex-Dependent Manner
264 c 2023-03-15
264 1b American Association for Cancer Research (AACR),c 2023
338 a print2 rdacarrier
520 a Sex-driven immune differences can affect tumor progression and the landscape of the tumor microenvironment. Deeper understanding of these differences in males and females can inform patient selection to improve sex-optimized immunotherapy treatments. In this study, single-cell RNA sequencing and protein analyses uncovered a subpopulation of myeloid cells in pancreatic lesions associated with an immune-excluded tumor phenotype and effector T-cell exhaustion exclusively in females. This myeloid subpopulation was positively correlated with poor survival and genetic signatures of M2-like macrophages and T-cell exhaustion in females. The G-protein coupled receptor formyl peptide receptor 2 (FPR2) mediated these immunosuppressive effects. In vitro, treatment of myeloid cells with a specific FPR2 antagonist prevented exhaustion and enhanced cytotoxicity of effector cells. Proteomic analysis revealed high expression of immunosuppressive secretory proteins PGE2 and galectin-9, enriched integrin pathway, and reduced proinflammatory signals like TNFα and IFNγ in female M2-like macrophages upon FPR2 agonist treatment. In addition, myeloid cells treated with FPR2 agonists induced TIM3 and PD-1 expression only in female T cells. Treatment with anti-TIM3 antibodies reversed T-cell exhaustion and stimulated their ability to infiltrate and kill pancreatic spheroids. In vivo, progression of syngeneic pancreatic tumors was significantly suppressed in FPR2 knockout (KO) female mice compared with wild-type (WT) female mice and to WT and FPR2 KO male mice. In female mice, inoculation of tumors with FPR2 KO macrophages significantly reduced tumor growth compared with WT macrophages. Overall, this study identified an immunosuppressive function of FPR2 in females, highlighting a potential sex-specific precision immunotherapy strategy.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng
653 a Pancreatic Tumor Microenvironment
653 a T-cell Exhaustion
653 a Sex-Dependent Manner
7001 a Tay, Apple H.M.u Department of Biological Science, Nanyang Technological University, Singapore (SGP); Department of Oncology–Pathology, Karolinska Institute, Stockholm(SWE)4 aut
7001 a Calandigary, Ahmedu Department of Immunology, Genetics, and Pathology, Clinical Immunology, Uppsala (SWE)4 aut
7001 a Malki, Enanau Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm (SWE)4 aut
7001 a Suzuki, Sayakau Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm (SWE)4 aut
7001 a Liu, Tianjieu Department of Urology, First affiliated hospital of Xi'an Jiaotong university, Xi'an, Shaanxi (CHN)4 aut
7001 a Wang, Qiu Department of Urology, First affiliated hospital of Xi'an Jiaotong university, Xi'an, Shaanxi (CHN)4 aut
7001 a Fernández-Moro, Carlosu Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm (SWE)4 aut
7001 a Kaisso, Marinau Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm (SWE)4 aut
7001 a Olofsson-Sahl, Peteru Högskolan Väst,Grants and Innovation Office (GIO),Pronoxis AB, Medicon Village, Lund (SWE)4 aut0 (Swepub:hv)u050742
7001 a Melssen, Maritu Department of Immunology, Genetics and Pathology, Vascular Biology, Uppsala (SWE)4 aut
7001 a Sze, Siu Kwanu Department of Biological Science, Nanyang Technological University, Singapore (SGP); Department of Health Sciences, Faculty of Applied Health Sciences, Brock University, Ontario (CAN)4 aut
7001 a Björnstedt, Mikaelu Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm (SWE)4 aut
7001 a Löhr, Matthias J.u Department of Clinical Science, Intervention and Technology, Pancreatic Cancer Research Laboratory, Karolinska Institutet, Stockholm (SWE)4 aut
7001 a Karlsson, Mikael C.I.u Department of Microbiology, Tumor and Cell Biology, Karolinska Insitutet, Stockholm (SWE)4 aut
7001 a Heuchel, Raineru Department of Clinical Science, Intervention and Technology, Pancreatic Cancer Research Laboratory, Karolinska Institutet, Stockholm (SWE)4 aut
7001 a Sarhan, Dhifafu Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm (SWE)4 aut
7102 a Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm (SWE); Department of Urology, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou (CHN)b Department of Biological Science, Nanyang Technological University, Singapore (SGP); Department of Oncology–Pathology, Karolinska Institute, Stockholm(SWE)4 org
7730 t Cancer Researchd : American Association for Cancer Research (AACR)g 83:10, s. 1628-1645q 83:10<1628-1645x 0008-5472x 1538-7445
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:hv:diva-21403
8564 8u https://doi.org/10.1158/0008-5472.can-22-2932

Hitta via bibliotek

Till lärosätets databas

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy