Natural Killer Cell Subsets in Hematological Diseases: Learning

Total Page:16

File Type:pdf, Size:1020Kb

Natural Killer Cell Subsets in Hematological Diseases: Learning Natural Killer cell subsets in hematological diseases : learning for immunotherapy Dang Nghiem Vo To cite this version: Dang Nghiem Vo. Natural Killer cell subsets in hematological diseases : learning for immunotherapy. Human health and pathology. Université Montpellier, 2018. English. NNT : 2018MONTT013. tel- 01868212 HAL Id: tel-01868212 https://tel.archives-ouvertes.fr/tel-01868212 Submitted on 5 Sep 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. THÈSE POUR OBTENIR LE GRADE DE DOCTEUR DE L’UNIVERSITÉ DE M ONTPELLIER En Biologie Santé École doctorale CBS2 n°168 - Sciences Chimiques et Biologiques pour la Santé Unité de recherche INSERM U1183 - Institut de Médecine Régénératrice et de Biothérapie (IRMB) Natural Killer cell subsets in hematological diseases : learning for immunotherapy Présentée par Dang Nghiem VO Le 03 Juillet 2018 Sous la direction de Dr. Martin VILLALBA-GONZALEZ Devant le jury composé de Prof. Marie-Alix POUL, PU, Institut de Recherche en Cancerologie de Montpellier (IRCM) Président du Jury Dr. Julian PARDO, DR, Biomedical Research Center of Aragon (CIBA), Zaragoza, Espagne Rapporteur Dr. Cyril FAURIAT, CR, Centre de Recherche en Cancérologie de Marseille (CRCM) Rapporteur Dr. Laurent GROS, CR, Institut de Recherche en Cancerologie de Montpellier (IRCM) Examinateur Dr. Brigitte KERFELEC, CR, Centre de Recherche en Cancérologie de Marseille (CRCM) Examinateur Dr. Martin VILLALBA-GONZALEZ, DR, Institut de Médecine Régénératrice et de Biothérapie (IRMB) Directeur de thèse ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! "6CFGOD87+8,8F-.! ! ! $GJ=EGKLg) ') OG,D.) DA0$) LG) '1230) E4) '1$&AK) 2.NAKGJg) 6#7) 82#LA3) 4ADD2-:9g) ;GJ) 1AK) ;GFLA3,G,K)K,HHGJL)'1JG,?1G,L)'1$)LAE$)G;)E4).16)KLM.47)6#7)4ADD2-:2)12&)2-O24K):$$3) H9LA$3'-4)K,HHGJLAN$);GJ)HJGNA.A3>)E$)?,A.23<$)23.);$$.:9;0)O1$3$5$#)3$<;$&K2#4);GJ) '1$)HJG?J$&K)G;)E4)OGJ0K)O1AD$)$3<G,J2>A3>)E$);GJ):$/3>)23)A3.=H$3.$3')J$&$2#;1$#7) 8GJ$"N$#g)1$)K1GO$.)E$)1GO)LG):$)HJG.,;LAN$)23.)$3BG4A3>)K;A$3<$)9L)'1$)K9E$)LAE$7) 5A'1G,L)E,;1)1$&AKL9LAGFg)');G,D.)K24)'19L)')12N=FnL):$$3)2:D$)LG)?G)'1AK);2#)A3)'1$).16) BG,J3$4)OA'1G,')1AK)?,A.23<$7) ) 1=;G3.D4g)')OG,D.)DA0$)LG)'1230)LG)2-D)E4)'1$&AK)B,J4)E=E:$#Ki).JG;7)82#A$EFDAP).G,Dg) 6#7)H2,J$3')IJGKg)6#7)J,DA23).2#.Gg)6#7)K4JAD)$2,JA9L)23.)6#7) JA?ALL=)M$#;$-=;g);GJ)'1$/J) 0A3.3$&K)A3)H2#LA;AH9LAG3)23.)$N2-,9LAG3)G;)E4).16)OGJ07)5A'1)KH=;A2-)'1230K)LG)6#) H2,J$3L)IJGK)23.)6#7)J,DA23).2#.G);GJ)'1$/J)N2-,2:D$).AK;,KKAG3)23.)K,??$&LAG3K).,JA3>) E4).16);GEEALL==)E$$'/3>K).,JA3>)E4).16)&LM.47) ) N3)'1$);GDDGO3>)3"L=g)')OG,D.)DA0$)LG)$GHJ$&K)E4)?J9LLALM.$);GJ)2-D)E4);GDD$2>,$&)23.) &$3/GJK)A3)G,J)L=9Eg)'08 EPI,AH$)Rg)AF;D,.A3>)6#7)J2NA$#)S$#323.$T()6$-H1A3$)IA'$324) t.1"ug) ,=J$2) FDD$3.$E9$>2) t.1"ug) K2'1$#A3$) FD$GA2) t.1"ug) 6/$>G) 123<1$TE82#LA3$T) t.1"ug)FE$-A$)KGJFADDG3)t.1"ug)F:J2#)3DES2Q)M123)t.1"ug)PO$-A32)MJT4OA3&02)t.1"u) ;GJ) '1$/J) 1$-H;,D) .AK;,KKAG3) 23.) ;JALA;2-) ;$$.:9;0) :,L) 2-KG) A3) L=;1FA;2-) 23.) .2/D4) DA;$) K,HHGJLK) 2#G,3.) '1$) :$3<1) .,JA3>) '1$) O1GD$) LAE$) G;) E4) .16) A3) '1$) D2:7) ') 9E) 2-KG) A3.$:L)LG)2-D)'1$)G'1$#);GDD$2>,$&)9L)'1$)A3&LALM'$)23.)D2:E2'$&);GJ)1$-HA3>)E$)A3)E234) .A;;$#$3')2&H=;LK)A3)23.)G,LKA.$)'1$)-2:7) ) $A32-D4g)')OG,D.)DA0$)LG)K2N$)'1$)D2&L)OGJ.K);GJ)E4)EGE)23.).2.);GJ)HJGNA.A3>)E$)'1$) :$&L) $.,;9LAG3) OA'1A3) '1$/J) ;9H2:DALAL4) .$&HA'$) E,LAHD$) .A;;A;,DLA$&7) 2G) E4) .2.g) ;GJ) 2-O24K) :$-A$NA3>) 23.) $3<G,J2>A3>) ;GJ) E4) H,JK,AL) G;) J$&$2#;1) ;2#$$#7) F3.) EGEg) ;GJ) :$-A$NA3>)AF)E$)#$>2#.D$&K)G;)E4).=;AKAG3)23.)1$#)$3.D$&K)K,HHGJ'7) ) ! ! "! /86D010-2GF!G3!42F0F620D!0677G1-.! ) F) H2#L) G;) '1AK) '1$&AK) OGJ0) O2&) K,HHGJ'$.) :4) 2) ;$-DGOK1H) HJGNA.$.) :4) 8AFAKL=J$) .$) Dn#3&$/?3$%$3')1,H$#/$,J)$').$)D2)0=;1$#;1$)t8P10u7)F)K=;G3.)H2#L)G;)'1AK)OGJ0)O2&) 0A3.D4) ;,3.$.) :4) KSXE8GFLH$-DA$#) ;GFLJ9;LK) NA2) J=;GEE$3.9LAG3) ;JGE) E4) '1$&AK) 2.NAKGJ7)21$);,3.A3>)2>$3<A$&).G)3"L)HD24)234)JGD$)A3).$&/>3)23.)AFL=HJ=L9LAG3)2&)O$-D) 2&).=;AKAGF)LG)H,:DAK1)G;)'1$)OGJ0K)HJ$&$3'$.)A3)'1AK)'1$&AK7) ) ) ) ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! #! 82.-!G3!765D2.:87!01-26D8.!2F!7881;18N28O87!BG61F0D.! ) Z7) MJT4OA3&02) P7g) FDD$3.$E9$>2) ,jg) KGJFADDG3) F7g) .:# $D(C g) K24J$;G,J;I) H7g) .232:A$#$&)K7g)4AD;1$&)K7g)6$<123$'E8$#NADD$)J7g)S/;1$#A)77g)0GKKA)J7$7g)K2#LJG3)I7g) 4ADD2-:2)87)'.=FLA;A;9LAG3)G;)FFLAE',EGJ)K$-DK)K2#J4A3>),9LMJ2-)MADD$#)t,)u)K$-D) FFLA?$3&) A3) .9LA$3'&) 5A'1) S$%9LGDG?A;2-) K23<$#K7) # >C%:9#(#): ) \g) Z]^R_Z]`^) t\aZbu7) ) \7) .:(# $D(C g) FD$GA2) K7g) FDD$3.$E9$>2) ,jg) 8GJK;12,K$#) $7g) S",GL) 07g) 8$32#.) K7g) 22#'$) M7g) K2#LJG3) I7g) 4ADD2-:2) 87) ,)) ;$-D) 9;LAN9LAG3) 23.) J=;GN$#4) G;) ,)) ;$-D) K,:K=LK)A3)D4EH1GE2)H9LA$3'&)2;L=J)G:A3,LMT,E9:)23.)D$32-A.GEA.$)LJ=9LE$3'7) -)8C>AA,)C-C./ 7).GAiZa7Zacar\Z^\Ra\e7\aZ`7ZRaf]\\)t\aZ`u7) ) ]7) 123<1$TE82#LA3$T)67g)FDD$3.$E9$>2),jg)NJ=;;1AGFA)17g)22-2#A;G)I7g)KGJFADDG3)F7g) .:#$D(C g)0$3$)K7g)H,)gE77g)MJT4OA3&02)P7g)F3$-)F7g)I2-N$T)P787g).2#.G)J7g)0G:$#L) 7g) 82#LA3$2,) .7g) S/;1$#A) 77g) $#LGDAFA) $7g) K2#LJG3) I7g) 4ADD2-:2) 87) PPH23&AG3) G;) 2-DG?$3$/;) ,)) ;$-DK) OA'1) $;;A;A$3') 9FLA:G.4E.=H$3.$3') ;$-D) ;4LGLGPA;AL4) 2>2/3&L) E,DLAHD$)',EGJK7) 11:23)C45>8F 7)t\aZcu7)tAF)HJ$&Ku) ) R7) M123)F7)3ES7g)FDD$3.$E9$>2),jg)IA'$324)67g)I$#:2-EK12-GA3)17g)IG3.$2,)K7g).:# "D(C g) $-021D2)17g)NJ=;;1AGFA)17g)22-2#A;G)I7g) $#LGDAFA)$7g) GRA;)87g)42-.ANA$-KG)J7) 87g) $BB23/)$7g)(9JA$-)'7g)HGH$TE8$BA2)'7)K7g)$2B2&)H7g)H=;$-DA$#)KES7g)S$#323.$T)J7g) 62,B9L)87g)4ADD2-:2)87)21$).6MZ)'31A:ALGJ)6/;1DGJG9;$'2'$)KGFLJGDK)K1GD$&L=JGD) S"E$"KL9KAK)21JG,?1)'1$)P0Mbr8P$\).2'1O247) 08>:)5#7>889:DC254 7)`g)Z_Zb)U\aZ`u7) ) b7) $-021D2) 17g) M123) F7) 3ES7g) IA'$324) 67g) FD$GA2) K7g) IG3.$2,) K7g) .:# $D(C g) -J=;;1AGFA) 17g) 22-2#A;G) I7g) $#LGDAFA) $7g) K2#LJG3) I7g) S$#323.$T) J7g) 62,B9LE K12N23/$,) 87g) FDD$3.$E9$>2) ,jg) 4ADD2-:2) 87) K123>$&) A3) E$'2:GDAKE) 2;;=;L) $GHJ$&KAG3) G;) F K) LJ23&HGJL=JK) '1JG,?1) P0Mb) 23.) .=H$3.A3>) G3) Hb]) KL9LMK7) -)8C532.:5 )fg)ZZZR_ZZ\f)t\aZcu7) ) ^7) M123) F7) 3ES7g) FDD$3.$E9$>2) ,jg) IA'$324) 67g) I2#2,.$) J7g) .:# $D(C g) $-012-2) 17g) I$#:2-EK12-GA3) 17g) IG3.$2,) K7g) 62,B9L) 87g) 6$-=LLJ$) K7g) NJ=;;1AGFA) 17g) 22-2#A;G) I7g) $#LGDAFA)$7g)F3$-)F7g)K,$TN2)J787g)PFJAI,$T)J7F7g)K2#LJG3)I7g)H=;$-DA$#)KES7g) S$#323.$T) J7g) 4ADD2-:2) 87) 8ALG;1GFJA2-) ;GEHD$G) ') 9;LANAL4) KA?32-K) 9FLAGPA.23') J=KHG3&$)'1JG,?1)P0Mb7) 08>:)5#7>889:DC254 7)t\aZcu7)tAF)HJ$&Ku) ! ! ! ! ! ! ! $! 034%7!'8!)'*D7*D! ! ,4CD.35D!00000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000!12 ! .4CE64!7E4CD3*D87%%7!000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000!19 ! ):,-0#.!10!%#+#.,)!'+0.,B1)0',+!00000000000000000000000000000000000000000000000000000000000000000000000000000000!DD ! 101 ! %7*7.3%!'E7.E87F!34'ED!D:7!866E*7!CICD76!3*I!8DC!5'6A'*7*D!0000000000000000000000000000000!D2 ! 10D ! +(!57%%!'*D'97*I!000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000!DM ! 102 ! +(!57%%!7IE53D8'*!3*I!D'%7.3*57!000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000!D_ ! 10M ! +(!57%%!.757AD'.!.7A7.D'8.7!3*I!C89*3%8*9!A3D:F3IC!0000000000000000000000000000000000000000000000000000000!22 ! 109 ! :'F!I'7C!3!+(!57%%!O8%%!8DC!D3.97DR!000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000!MD ! 10Q ! :E63*!+(!57%%!3*I!D:7!866E*7!5'*D.'%!'8!E8.3%!8*875D8'*!00000000000000000000000000000000000000000000!MM ! 10R ! 0E6'.!866E*'CE.E78%%3*57!8.'6!D:7!+(!57%%!A7.CA75D8E7S!DE6'.!866E*7!7E3C8'*! CD.3D7987C!000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000!M9 ! 10T ! !2#1(1, !7UA3*C8'*!'8!3%%'97*785!+(!57%%!8'.!53*57.!866E*'D:7.3AI!00000000000000000000000000!MT ! 10_ ! )BM9!7UA.7CC8'*!3*I!3%D7.*3D8E7!CA%858*9!8C'8'.6C!'*!+(!57%%!000000000000000000000000000000000000!91 ! 101V ! ,86C!3*I!CD.E5DE.7!'8!D:7!D:7C8C!0000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000!9M ! ):,-0#.!D0!W,0#.',)7!,+B!W#0:,B7!00000000000000000000000000000000000000000000000000000000000000000000000000000!9T ! D01!%,)#+!CDEIIS!0000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000!9_! D0D!,W)!CDEIIS!000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000!Q1 ! D02!:'2!CDEII!00000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000!QD ! D0M! '(#1(/., !+(!57%%!7UA3*C8'*!8.'6!:73%D:I!I'*'.!1) !0000000000000000000000000000000000000000000000000000000000000!QR ! ):,-0#.!20!0000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000!Q_
Recommended publications
  • Dimethyl Fumarate Or Any of the Excipients of TECFIDERA Safely and Effectively
    HIGHLIGHTS OF PRESCRIBING INFORMATION ___________________ CONTRAINDICATIONS ___________________ These highlights do not include all the information needed to use Known hypersensitivity to dimethyl fumarate or any of the excipients of TECFIDERA safely and effectively. See full prescribing information for TECFIDERA. (4) TECFIDERA. _______________ _______________ WARNINGS AND PRECAUTIONS TECFIDERA® (dimethyl fumarate) delayed-release capsules, for oral use • Anaphylaxis and angioedema: Discontinue and do not restart TECFIDERA Initial U.S. Approval: 2013 if these occur. (5.1) • Progressive multifocal leukoencephalopathy (PML): Withhold _________________ RECENT MAJOR CHANGES _________________ TECFIDERA at the first sign or symptom suggestive of PML. (5.2) Dosage and Administration, Blood Test Prior to • Lymphopenia: Obtain a CBC including lymphocyte count before initiating TECFIDERA, after 6 months, and every 6 to 12 months thereafter. Initiation of Therapy (2.2) 1/2017 9 Warnings and Precautions, PML (5.2) 2/2016 Consider interruption of TECFIDERA if lymphocyte counts <0.5 x 10 /L Warnings and Precautions, Liver Injury (5.4) 1/2017 persist for more than six months. (5.3) • Liver injury: Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels before initiating TECFIDERA and during treatment, __________________ INDICATIONS AND USAGE _________________ as clinically indicated. Discontinue TECFIDERA if clinically significant TECFIDERA is indicated for the treatment of patients with relapsing forms of liver injury induced by TECFIDERA is suspected. (5.4) multiple sclerosis (1) _______________ DOSAGE AND ADMINISTRATION ______________ ___________________ ADVERSE REACTIONS ___________________ • Starting dose: 120 mg twice a day, orally, for 7 days (2.1) Most common adverse reactions (incidence ≥10% and ≥2% placebo) were • Maintenance dose after 7 days: 240 mg twice a day, orally (2.1) flushing, abdominal pain, diarrhea, and nausea.
    [Show full text]
  • COMPARISON of the WHO ATC CLASSIFICATION & Ephmra/Intellus Worldwide ANATOMICAL CLASSIFICATION
    COMPARISON OF THE WHO ATC CLASSIFICATION & EphMRA/Intellus Worldwide ANATOMICAL CLASSIFICATION: VERSION June 2019 2 Comparison of the WHO ATC Classification and EphMRA / Intellus Worldwide Anatomical Classification The following booklet is designed to improve the understanding of the two classification systems. The development of the two systems had previously taken place separately. EphMRA and WHO are now working together to ensure that there is a convergence of the 2 systems rather than a divergence. In order to better understand the two classification systems, we should pay attention to the way in which substances/products are classified. WHO mainly classifies substances according to the therapeutic or pharmaceutical aspects and in one class only (particular formulations or strengths can be given separate codes, e.g. clonidine in C02A as antihypertensive agent, N02C as anti-migraine product and S01E as ophthalmic product). EphMRA classifies products, mainly according to their indications and use. Therefore, it is possible to find the same compound in several classes, depending on the product, e.g., NAPROXEN tablets can be classified in M1A (antirheumatic), N2B (analgesic) and G2C if indicated for gynaecological conditions only. The purposes of classification are also different: The main purpose of the WHO classification is for international drug utilisation research and for adverse drug reaction monitoring. This classification is recommended by the WHO for use in international drug utilisation research. The EphMRA/Intellus Worldwide classification has a primary objective to satisfy the marketing needs of the pharmaceutical companies. Therefore, a direct comparison is sometimes difficult due to the different nature and purpose of the two systems.
    [Show full text]
  • Hpra Drug Safety 66Th Newsletter Edition
    FEBRUARY 2015 HPRA DRUG SAFETY 66TH NEWSLETTER EDITION 3 Mycophenolate mofetil (CellCept) and 4 Direct Healthcare Professional In this Edition Mycophenolic acid (Myfortic) - New warnings Communications published on about the risks of hypogammaglobulinaemia the HPRA website since the last 1 Eligard (leuprorelin acetate depot injection) and bronchiectasis Drug Safety Newsletter - Risk of lack of efficacy due to incorrect reconstitution and administration process 4 Tecfidera (dimethyl fumarate) - Progressive Multifocal Leukoencephalopathy (PML) has 2 Beta interferons – Risk of thrombotic occurred in a patient with severe microangiopathy and nephrotic syndrome and prolonged lymphopenia Eligard (leuprorelin acetate depot injection) - Risk of lack of efficacy due to incorrect reconstitution and administration process Following identification of a signal and safe treatment of patients with It is available in six-monthly (45mg), of administration errors with Eligard prostate cancer. Lack of efficacy may three-monthly (22.5mg) and one- and concerns that such errors may occur due to incorrect reconstitution monthly (7.5mg) formulations. In impact on clinical efficacy, this issue of Eligard. the majority of patients, androgen was reviewed at EU level by the deprivation therapy (ADT) with Eligard Eligard is indicated for the treatment Pharmacovigilance Risk Assessment results in testosterone levels below the of hormone dependent advanced Committee (PRAC). A cumulative standard castration threshold (<50ng/ prostate cancer and for the treatment review of reported global cases dL; <1.7 nmol/L); and in most cases, of high risk localised and locally identified errors related to storage, patients reach testosterone levels advanced hormone dependent preparation and reconstitution of below <20ng/dL. prostate cancer in combination Eligard.
    [Show full text]
  • Trogocytosis of Peptide–MHC Class II Complexes from Dendritic Cells Confers Antigen-Presenting Ability on Basophils
    Trogocytosis of peptide–MHC class II complexes from dendritic cells confers antigen-presenting ability on basophils Kensuke Miyakea, Nozomu Shiozawaa, Toshihisa Nagaoa, Soichiro Yoshikawaa, Yoshinori Yamanishia, and Hajime Karasuyamaa,1 aDepartment of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan Edited by Ruslan Medzhitov, Yale University School of Medicine, New Haven, CT, and approved December 7, 2016 (received for review September 26, 2016) Th2 immunity plays important roles in both protective and allergic function as antigen-presenting cells (APCs) and induce Th2 dif- responses. Nevertheless, the nature of antigen-presenting cells ferentiation in cooperation with basophil-derived IL-4. responsible for Th2 cell differentiation remains ill-defined com- Reports from three independent groups further expanded the pared with the nature of the cells responsible for Th1 and Th17 cell role for basophils in Th2 differentiation and demonstrated in differentiation. Basophils have attracted attention as a producer of three distinct experimental settings that basophils, rather than Th2-inducing cytokine IL-4, whereas their MHC class II (MHC-II) DCs, are the critical APCs for driving Th2 differentiation (5–7). expression and function as antigen-presenting cells are matters of In all settings, basophils expressed both MHC class II (MHC-II) considerable controversy. Here we revisited the MHC-II expression and costimulatory molecules (CD80, CD86, or CD40) necessary for on basophils and explored its functional relevance in Th2 cell APC function, and could process and present antigens. Depletion differentiation. Basophils generated in vitro from bone marrow of basophils but not DCs abolished Th2 differentiation in vivo.
    [Show full text]
  • Dimethyl Fumarate and Progressive Multifocal Leucoencephalopathy (PML)
    Dimethyl fumarate and progressive multifocal leucoencephalopathy (PML) Introduction Dimethyl fumarate Psorinovo® is not registered through the Medicines Evaluation Board (MEB). It is a compounded drug made by GMP compounding pharmacy Mierlo Hout in the Netherlands, and used for the indication psoriasis [1]. Psorinovo® has been compounded by pharmacy Mierlo Hout for 28 years. According to Dutch law Mierlo Hout pharmacy is regarded as a supplying-pharmacy. ® Dimethyl fumarate, registered as Tecfidera , was granted marketing authorization in the Netherlands on 30 January 2014 and is indicated for the treatment of adult patients with relapsing remitting multiple sclerosis [2]. Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system caused by reactivation of the polyomavirus JC (JC virus). Asymptomatic primary infection with the JC virus occurs in childhood, antibodies can be found in 86% of adults. PML occurs almost exclusively in immunosuppressed individuals. There were only isolated cases reported of PML in patients without apparent immunosuppression. However, there are reports of PML affecting patients who have conditions associated with minimal or occult immunosuppression, such as hepatic cirrhosis and renal failure [3]. PML has also been reported in patients treated with drugs such as belatacept, brentuximab, efalizumab, fludarabine, glucocorticoids, infliximab, mycophenolate, rituximab, ruxolitinib and natalizumab. In some cases, these drugs were used in combination with other immunosuppressive medications (eg, cyclophosphamide, leflunomide, methotrexate). Many of the patients had an underlying hematologic malignancy or collagen vascular disease [3]. There is no specific treatment for PML. The main approach is restoring the host adaptive immune response, a strategy that appears to prolong survival.
    [Show full text]
  • PD-L1 and B7-1 Cis-Interaction: New Mechanisms in Immune Checkpoints and Immunotherapies
    Trends in Molecular Medicine Opinion PD-L1 and B7-1 Cis-Interaction: New Mechanisms in Immune Checkpoints and Immunotherapies Christopher D. Nishimura,1,6 Marc C. Pulanco,1,6 Wei Cui,2 Liming Lu,3 and Xingxing Zang1,4,5,* Immune checkpoints negatively regulate immune cell responses. Programmed Highlights cell death protein 1:programmed death ligand 1 (PD-1:PD-L1) and cytotoxic Dysregulation of immune checkpoints T lymphocyte-associated protein 4 (CTLA-4):B7-1 are among the most important contributes to the pathogenesis of immune checkpoint pathways, and are key targets for immunotherapies that cancer, autoimmunity, and organ trans- plant rejection by mediating undesired seek to modulate the balance between stimulatory and inhibitory signals to lead immune responses. to favorable therapeutic outcomes. The current dogma of these two immune checkpoint pathways has regarded them as independent with no interactions. The limited long-term therapeutic effi- However, the newly characterized PD-L1:B7-1 ligand–ligand cis-interaction and cacy of immunotherapies targeting immune checkpoints underscores the its ability to bind CTLA-4 and CD28, but not PD-1, suggests that these pathways need to better understand the underlying have significant crosstalk. Here, we propose that the PD-L1:B7-1 cis-interaction biology of these proteins. brings novel mechanistic understanding of these pathways, new insights into – mechanisms of current immunotherapies, and fresh ideas to develop better Immune checkpoint receptor ligand interactions most commonly occur in treatments in a variety of therapeutic settings. trans (e.g., the receptor and ligand are expressed on two different cells). The newly characterized PD-L1:B7-1 interac- tion occurs in cis (e.g., the receptor and Immune Checkpoint Blockade ligandareexpressedonthesamecell).
    [Show full text]
  • Investigating the Role of CR3 in Trogocytosis of Trichomonas Vaginalis Cells by Neutrophil-Like Cells
    Investigating the role of CR3 in trogocytosis of Trichomonas vaginalis cells by Neutrophil-like cells. Senior Thesis California State Polytechnic University, Department of Biology Aljona Leka Team Members: Jose Moran Mercer Lab Spring 2020 Table of Contents 1. Abstract 2. Introduction 3. Results a) PLB-985 cells differentiate into Neutrophil-like cells b) Strategy for functional deletion of CD11b c) Generation of CD11b knockout cell lines with CRISPR-Cas9 gene editing system showed low cell viability post transfection d) NLCs kill T. vaginalis in the presence of human serum e) NLCs kill T. vaginalis in the presence of heat inactivated human serum 4. Methods a. Promyelocytic cell lines and culture b. Immunolabeling for CD11b and CD18 c. Generation of genetically modified cells d. Culturing transfectants e. Single cell dilution f. Culturing T. vaginalis cells g. Cytotoxicity assay h. Plasmid Construction i. Isolating the px459construct for transfection 5. Discussion 6. References 7. Acknowledgements 8. Supporting information Abstract Trichomonas vaginalis (T. vaginalis) causes the non-viral sexually transmitted infection (STI), trichomoniasis. Trichomoniasis affected almost 276.4 million people globally in 2008 alone, with most incidents occurring in underserved communities. The main curative treatment for T. vaginalis is an antibiotic, Metronidazole, though antibiotic resistance is on the rise. Neutrophils are the first responders against T. vaginalis, killing the parasite through a recently discovered process called trogocytosis, in which the neutrophils “nibble” on the parasite’s membrane leading to killing of the parasite. However, current literature lacks the knowledge of which molecular components are involved in trogocytosis of T. vaginalis. Trogocytosis is a contact- dependent process mediated through opsonins, specifically iC3b, which serves as a tag to make the pathogens “tasty” for the neutrophils.
    [Show full text]
  • Patent No.: US 8952006 B2
    USOO8952006B2 (12) United States Patent (10) Patent No.: US 8,952,006 B2 Cundy et al. (45) Date of Patent: *Feb. 10, 2015 (54) MORPHOLINOALKYL FUMARATE FOREIGN PATENT DOCUMENTS COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE W. wo.5: 886 WO WO O2/O55063 T 2002 (71) Applicant: XenoPort, Inc., Santa Clara, CA (US) WO WO O2/O55066 T 2002 WO WOO3,087.174 10, 2003 (72) Inventors: Kenneth C. Cundy, Redwood City, CA WO WO 2005/023241 3, 2005 WO WO 2005/027899 3, 2005 (US); Suresh K. Manthati, Sunnyvale, WO WO 2006/037342 4/2006 CA (US); David J. Wustrow, Los Gatos, WO WO 2006/122652 11, 2006 CA (US) WO WO 2007/042034 4/2007 WO 2010/022177 A2 2, 2010 (73) Assignee: XenoPort, Inc., Santa Clara, CA (US) WO 2014/0964.25 A2 6, 2014 (*) Notice: Subject to any disclaimer, the term of this OTHER PUBLICATIONS patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days. Cecil Textbook of Medicine, 20th edition (1996), vol. 2, pp. 2050 2057.* spent is Subject to a terminal dis- Cecil Textbook of Medicine, 20th edition (1996), vol. 2, pp. 1992 1996.* (21) Appl. No.: 13/761,864 Ey's statisfy it to (22) Filed: Feb. 7, 2013 com/2003/HEALTH/conditions/09/24/alzheimers.drug.ap/index. e f 9 html>. (65) Prior Publication Data Atreya et al., NF-kB in inflammatory bowel disease, J Intern Med (2008), 263(6): 591-6. US 2013/02O3753 A1 Aug. 8, 2013 Bardgett et al., NMDA receptor blockade and hippocampal neuronal loss impair fear conditioning and position habit reversal in C57B1/6 mice, Brain Res Bull (2003), 60: 131-142.
    [Show full text]
  • T Cells Via Trogocytosis + Apcs Onto CD8 Programmed Death Ligand 1
    Antigen-Specific Transfer of Functional Programmed Death Ligand 1 from Human APCs onto CD8+ T Cells via Trogocytosis This information is current as Regina Gary, Simon Voelkl, Ralf Palmisano, Evelyn Ullrich, of October 1, 2021. Jacobus J. Bosch and Andreas Mackensen J Immunol 2012; 188:744-752; Prepublished online 14 December 2011; doi: 10.4049/jimmunol.1101412 http://www.jimmunol.org/content/188/2/744 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2011/12/14/jimmunol.110141 Material 2.DC1 http://www.jimmunol.org/ References This article cites 44 articles, 23 of which you can access for free at: http://www.jimmunol.org/content/188/2/744.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on October 1, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2012 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Antigen-Specific Transfer of Functional Programmed Death Ligand 1 from Human APCs onto CD8+ T Cells via Trogocytosis Regina Gary,* Simon Voelkl,* Ralf Palmisano,† Evelyn Ullrich,* Jacobus J.
    [Show full text]
  • The Age-Related Efficacy of Dimethyl Fumarate and Natalizumab in the Real-World Management of Multiple Sclerosis
    pharmaceuticals Article The Age-Related Efficacy of Dimethyl Fumarate and Natalizumab in the Real-World Management of Multiple Sclerosis Roberto De Masi 1,2 , Stefania Orlando 1,* and Antonella De Donno 3 1 Laboratory of Neuroproteomics, Multiple Sclerosis Centre, “F. Ferrari” Hospital, 73042 Casarano, Lecce, Italy; [email protected] 2 Complex Operative Unit of Neurology, “F. Ferrari” Hospital, 73042 Casarano, Lecce, Italy 3 Laboratory of Hygiene, Department of Biological and Environmental Sciences and Technologies, University of the Salento, 73100 Lecce, Italy; [email protected] * Correspondence: [email protected]; Tel.: +39-0833-508-412 Abstract: We investigated the comparative age-related efficacy of dimethyl fumarate (DMF) and natalizumab (NTZ) in clinical practice on multiple sclerosis (MS). Research in this area is lacking in the previous literature. In a three-year retrospective and clinical–paraclinical study, we compared 173 DMF patients and 94 NTZ patients with a similar average age (40 years) and disease duration (DD) (10 years). Expanded Disability Status Scale (EDSS) scores were higher in the NTZ group than in the DMF group at 3.5 vs. 2.5, respectively (p = 0.001). However, in both groups, age values correlated with DD (r = 0.42; p < 0.001), EDSS (r = 0.52; p < 0.001) and age at onset (r = 0.18; p < 0.001). Furthermore, age-adjusted Kaplan–Meier curves showed that NTZ-treated subjects maintained a 1.0–3.0 EDSS status score (p = 0.003) more frequently and a 3.5–7.0 score (p = 0.022) significantly less frequently compared with DMF-treated subjects.
    [Show full text]
  • Trogocytosis of Peptide–MHC Class II Complexes from Dendritic Cells Confers Antigen-Presenting Ability on Basophils
    Trogocytosis of peptide–MHC class II complexes from dendritic cells confers antigen-presenting ability on basophils Kensuke Miyakea, Nozomu Shiozawaa, Toshihisa Nagaoa, Soichiro Yoshikawaa, Yoshinori Yamanishia, and Hajime Karasuyamaa,1 aDepartment of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan Edited by Ruslan Medzhitov, Yale University School of Medicine, New Haven, CT, and approved December 7, 2016 (received for review September 26, 2016) Th2 immunity plays important roles in both protective and allergic function as antigen-presenting cells (APCs) and induce Th2 dif- responses. Nevertheless, the nature of antigen-presenting cells ferentiation in cooperation with basophil-derived IL-4. responsible for Th2 cell differentiation remains ill-defined com- Reports from three independent groups further expanded the pared with the nature of the cells responsible for Th1 and Th17 cell role for basophils in Th2 differentiation and demonstrated in differentiation. Basophils have attracted attention as a producer of three distinct experimental settings that basophils, rather than Th2-inducing cytokine IL-4, whereas their MHC class II (MHC-II) DCs, are the critical APCs for driving Th2 differentiation (5–7). expression and function as antigen-presenting cells are matters of In all settings, basophils expressed both MHC class II (MHC-II) considerable controversy. Here we revisited the MHC-II expression and costimulatory molecules (CD80, CD86, or CD40) necessary for on basophils and explored its functional relevance in Th2 cell APC function, and could process and present antigens. Depletion differentiation. Basophils generated in vitro from bone marrow of basophils but not DCs abolished Th2 differentiation in vivo.
    [Show full text]
  • CVS Specialty® Pharmacy Distribution Drug List Providing One of the Broadest Offerings of Specialty Pharmaceuticals in the Industry
    July 2021 Updated Quarterly CVS Specialty® Pharmacy Distribution Drug List Providing one of the broadest offerings of specialty pharmaceuticals in the industry The CVS Specialty Pharmacy Distribution Drug List is a guide of medications available and distributed through CVS Specialty. Our goal is to help make your life better. With more than 40 years of experience, CVS Specialty provides quality care and service. Our network of pharmacies includes certifications and accreditations from the Joint Commission, Utilization Review Accreditation Commission (URAC), the National Association of Boards of Pharmacy (NABP) and the Accreditation Commission for Health Care (ACHC). These nationally recognized symbols reflect an organization’s commitment to meet highest standards of quality, compliance and safety. This list is updated quarterly. Below brand-name products are in CAPS, and generic products are shown in lowercase italics. Prospective Patients: Ready to get started? Enroll to get your medications from CVS Specialty. Health Care Providers: Visit the CVS Specialty website to download enrollment forms or call 1-800-237-2767 (TTY: 711). Therapy Class Brand Name Generic Name Acromegaly BYNFEZIA PEN octreotide acetate (SANDOSTATIN) SANDOSTATIN SANDOSTATIN LAR SOMATULINE DEPOT SOMAVERT Alcohol/Opioid Dependency PROBUPHINE IMPLANT KIT SUBLOCADE VIVITROL Allergen Immunotherapy ORALAIR PALFORZIA Alpha-1 Antitrypsin Deficiency ARALAST NP GLASSIA ZEMAIRA Amyloidosis ONPATTRO VYNDAMAX VYNDAQEL Anemia ARANESP EPOGEN PROCRIT REBLOZYL RETACRIT Asthma CINQAIR DUPIXENT FASENRA NUCALA XOLAIR Atopic Dermatitis DUPIXENT Botulinum Toxins DYSPORT MYOBLOC XEOMIN Cardiac Disorders ARCALYST dofetilide (TIKOSYN) TIKOSYN Specialty and non-specialty products distributed by CVS Specialty, as well as products covered by a member’s prescription or medical benefit plan, may change from time to time.
    [Show full text]