{"id":851,"date":"2019-03-17T22:22:25","date_gmt":"2019-03-17T19:22:25","guid":{"rendered":"http:\/\/blog.ulubat.org\/?p=851"},"modified":"2019-03-17T22:35:07","modified_gmt":"2019-03-17T19:35:07","slug":"mucizeye-yolculuk-1","status":"publish","type":"post","link":"https:\/\/blog.ulubat.org\/index.php\/genel\/mucizeye-yolculuk-1\/","title":{"rendered":"MUC\u0130ZEYE YOLCULUK-1"},"content":{"rendered":"\n

Sevgili okur! Son y\u0131llarda t\u0131p d\u00fcnyas\u0131nda kanser\ntedavisi ile ilgili ge\u00e7mi\u015fe k\u0131yasla mucize olarak nitelendirebilece\u011fimiz\ngeli\u015fmeler ya\u015fand\u0131. Hi\u00e7 ku\u015fkusuz bu mucizelerin kayna\u011f\u0131 2011 ve 2018 nobel t\u0131p\n\u00f6d\u00fcllerine konu olan ve bundan sonra da nobel \u00f6d\u00fcl\u00fc almaya devam etmesi\nbeklenen imm\u00fcnoterapilerdir. <\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

         \u0130mm\u00fcnoterapiler,\nimm\u00fcn sistemi kullanarak kanseri tedavi etme ilkesine dayan\u0131r. Tabi imm\u00fcnoterapileri\nanlayabilmek i\u00e7in \u00f6ncelikle k\u0131saca imm\u00fcn sistemimizden bahsedece\u011fim. Ama \u015funu\nda belirtmeliyim ki t\u00fcm yaz\u0131 boyunca anlatacaklar\u0131m, daha anla\u015f\u0131l\u0131r olmas\u0131 i\u00e7in\nhep konunun basitle\u015ftirilmi\u015f halleridir. \u0130leri okumalar i\u00e7in kaynak\u00e7amdan\nyararlanabilirsiniz. <\/p>\n\n\n\n

         \u0130mm\u00fcn sistemimizin en bilinen g\u00f6revi\nv\u00fccudumuzu patojen mikroorganizmalara kar\u015f\u0131 korumakt\u0131r. Bunu da do\u011fal imm\u00fcn\nsistemin bile\u015fenleri (makrofaj, dendritik h\u00fccre, n\u00f6trofil, NK h\u00fccresi,\nkompleman aktivasyonu vs.) ve antijen sunumuyla aktiflenen edinsel imm\u00fcn sistem\nbile\u015fenleri (B ve T lenfositler) sayesinde yapar (\u015eekil 1). <\/p>\n\n\n\n

\u015eekil\n1.<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

         \u0130mm\u00fcn\nsistemin olduk\u00e7a kar\u0131\u015f\u0131k ve hen\u00fcz tam olarak netli\u011fe kavu\u015fturulamam\u0131\u015f edinsel\nyan\u0131t\u0131n\u0131n beyni T h\u00fccreleridir. Hatta daha \u00f6zg\u00fcn konu\u015fmak gerekirse T helper h\u00fccreleridir.\nKemik ili\u011finde \u00fcretildikten sonra timusta olgunla\u015fan ve lenf nodlar\u0131nda inaktif\nolarak bekleyen T h\u00fccreleri kendilerine MHC\u2019ler (Major Histokompabilite\nKompleks) arac\u0131l\u0131\u011f\u0131yla antijen sunulunca aktifle\u015fir. Sunulan antijen \u00f6z antijen\nde olabilir \u00f6z olmayan bir antijen de olabilir. \u015eayet \u00f6z olmayan antijen\npatojen de\u011filse (\u00f6r: polen) g\u00fc\u00e7l\u00fc bir imm\u00fcn yan\u0131t olu\u015fmamas\u0131 gerekir. Olu\u015fmas\u0131\nhalinde alerjik hastal\u0131klar ortaya \u00e7\u0131kar. \u00d6z olmayan antijen patojen (\u00d6r:\nstreptokok antijeni) ise bu kez imm\u00fcn yan\u0131t geli\u015fmelidir aksi halde enfeksiyon\nhastal\u0131klar\u0131 ortaya \u00e7\u0131kar. \u015eayet sunulan antijen \u00f6z antijense ve patojenik\nde\u011filse (\u00d6r: Pankreas beta h\u00fccrelerinde bulunan GAD65 antijeni) imm\u00fcn yan\u0131t\nolu\u015fmamal\u0131d\u0131r. Olu\u015fmas\u0131 halinde tip 1 DM gibi otoimm\u00fcn hastal\u0131klar ortaya\n\u00e7\u0131kar. \u00d6z olmayan antijen patojenik ise (\u00d6r: kanser antijeni) imm\u00fcn yan\u0131t\ngeli\u015fmelidir. Aksi halde \u00f6rnek olarak kanser hastal\u0131\u011f\u0131 geli\u015febilir (\u015eekil 2). <\/p>\n\n\n\n

\u015eekil\n2.<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

        Asl\u0131nda buraya kadar anlatt\u0131\u011f\u0131m \u015feyler hep \u201cimm\u00fcn sistemimiz kanser h\u00fccreleri ile de m\u00fccadele eder\u201d c\u00fcmlesine altyap\u0131 haz\u0131rlamak i\u00e7indi. Bu arada k\u00fc\u00e7\u00fck bir antrparantez (yanl\u0131\u015f okumad\u0131n\u0131z antrparantez) a\u00e7mak istiyorum. Bilimde bilhassa da t\u0131pta okudu\u011fumuz, duydu\u011fumuz bilgileri hep nas\u0131l, neden gibi sorularla sorgulamal\u0131y\u0131z. Bilim de t\u0131p da ancak bu \u015fekilde geli\u015fir. Ben sizin yerinize birka\u00e7 soru sorup basit\u00e7e cevaplayaca\u011f\u0131m. Kalan sorular\u0131 sormak ve cevaplar\u0131n\u0131 bulmak size kald\u0131. <\/p>\n\n\n\n

         Peki\nnas\u0131l oluyor da ki\u015finin imm\u00fcn sistemi sa\u011flam olmas\u0131na ra\u011fmen kanser hastal\u0131\u011f\u0131\ngeli\u015febiliyor? Bunun bir\u00e7ok cevab\u0131 var ama en genel \u015fekilde cevab\u0131 kanserin\nkendisini imm\u00fcn sistemimizden saklamas\u0131d\u0131r. Peki kanser imm\u00fcn sistemden nas\u0131l\nsaklan\u0131yor? Hangi mekanizmalar bunda rol oynuyor? Bu da kabaca 3 \u015fekilde\noluyor: <\/p>\n\n\n\n

-\u0130mm\u00fcn sistemi kendi lehine \u00e7al\u0131\u015ft\u0131r\u0131yor.<\/p>\n\n\n\n

-\u0130mm\u00fcn sistemin kendine ula\u015fmas\u0131n\u0131 engelliyor.<\/p>\n\n\n\n

-\u0130mm\u00fcn sistemi bask\u0131l\u0131yor.<\/p>\n\n\n\n

        \u015eimdi biraz daha detaya inelim. Kanser h\u00fccreleri dokuda bulunan ve imm\u00fcn yan\u0131tta kilit rol oynayan makrofajlar\u0131 TAM\u2019lara (Tumor associated macrophages) \u00e7eviriyor. TAM\u2019lar bir nevi M2\u2019ler (alternatif makrofajlar) gibi davran\u0131p imm\u00fcn h\u00fccrelerin girmekte zorlanaca\u011f\u0131 bir kanser mikro\u00e7evresi olu\u015fmas\u0131na katk\u0131da bulunuyorlar. Bu mikro\u00e7evre hem asidik hem de hipoksik oldu\u011fu i\u00e7in T h\u00fccreleri burada ya\u015famakta zorlan\u0131yor. Ayr\u0131ca Proinflamatuar sinyalleri keserek de t\u00fcm\u00f6r\u00fc imm\u00fcn yan\u0131ttan koruyorlar. \u0130mm\u00fcn yan\u0131tta bir di\u011fer kilit rol oynayan h\u00fccre ise dendritik h\u00fccrelerdir. Kanser h\u00fccreleri salg\u0131lad\u0131klar\u0131 molek\u00fcller ile dendritik h\u00fccrelerinin olgunla\u015fmas\u0131n\u0131 engelleyerek kendisine bir edinsel imm\u00fcn yan\u0131t geli\u015fmesini \u00f6nlemeye \u00e7al\u0131\u015f\u0131yor. Ayr\u0131ca kanser h\u00fccreleri kendisine ula\u015fmay\u0131 ba\u015faran T h\u00fccrelerinin PD1 (programl\u0131 \u00f6l\u00fcm 1) resept\u00f6rlerine, \u00fcretti\u011fi PD ligandlar\u0131 ile ba\u011flanarak T h\u00fccrelerini apoptoza s\u00fcr\u00fckl\u00fcyor (\u015eekil 3). Kanser h\u00fccrelerinin imm\u00fcn yan\u0131ttan ka\u00e7\u0131\u015fta kulland\u0131\u011f\u0131 di\u011fer mekanizmalar ise Treg (Bask\u0131lay\u0131c\u0131 T h\u00fccre) say\u0131s\u0131n\u0131 ve antijen sunan h\u00fccrelerdeki B7 resept\u00f6r ailelerine ba\u011flanarak antijen sunumunu \u00f6nleyen CTLA-4 (Sitotoksik T Lenfositle \u0130li\u015fkili Antijen) resept\u00f6rlerinin say\u0131s\u0131n\u0131 art\u0131rmakt\u0131r (\u015eekil 4). Tabi bu yazd\u0131klar\u0131m d\u0131\u015f\u0131nda onlarca mekanizma daha var ama meram\u0131m\u0131 anlatabildi\u011fimi d\u00fc\u015f\u00fcnerek burada kesiyorum.<\/p>\n\n\n\n

\u015eekil 3. <\/p>\n\n\n\n

\"\"

Seidel JA ve ark. yazd\u0131\u011f\u0131 \u201cAnti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations\u201d makalesinden al\u0131nm\u0131\u015ft\u0131r.\ufeff<\/em> <\/figcaption><\/figure>\n\n\n\n

\u015eekil 4. <\/p>\n\n\n\n

\"\"

Seidel JA ve ark. yazd\u0131\u011f\u0131 \u201cAnti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations\u201d makalesinden al\u0131nm\u0131\u015ft\u0131r.\ufeff<\/em> <\/figcaption><\/figure>\n\n\n\n

        \u0130\u015fte \u015fimdi as\u0131l can al\u0131c\u0131 noktaya geliyoruz. Yukar\u0131da bahsetti\u011fim mekanizmalar\u0131n ke\u015ffinin ard\u0131ndan bu mekanizmalar\u0131 by-pass ederek imm\u00fcn sistemimizin tekrardan kanser h\u00fccresine sald\u0131rmas\u0131n\u0131 sa\u011flayabilece\u011fimiz anla\u015f\u0131ld\u0131. Ve bunun \u00fczerine bu mekanizmalar\u0131 by-pass edici tedavi modaliteleri geli\u015ftirildi. Bunlardan 3\u2019\u00fc 2011 ve 2018 y\u0131llar\u0131nda nobel fizyoloji\/t\u0131p \u00f6d\u00fcl\u00fcne lay\u0131k g\u00f6r\u00fcld\u00fc. B\u00fcy\u00fck ihtimalle yeni nobel \u00f6d\u00fclleri de yolda, at\u0131n fava bekleyin \ud83d\ude42        <\/p>\n\n\n\n

         Bir\nsonraki yaz\u0131mda imm\u00fcnoterapilerin tarih\u00e7esinden, \u00e7e\u015fitlerinden, klinikte\nkullan\u0131mlar\u0131ndan ve gelecek hedeflerinden bahsedece\u011fim. Sa\u011fl\u0131cakla ve bilimle\nkal\u0131n.<\/p>\n\n\n\n

Kaynak\u00e7a:<\/strong><\/p>\n\n\n\n

  1. Abbas AK, Lichtman AH Shiv P. Temel \u0130mm\u00fcnoloji. G\u00fcne\u015f T\u0131p Kitabevleri. 2015<\/li>
  2. Balkwill FR, Capasso M, Hagemann T. The tumor microenvironment at a glance. Journal of Cell Science. 2012 <\/li>
  3. Wang M, Zhao J, Zhang L, et al. Role of tumor microenvironment in tumorigenesis. Journal of Cancer. 2017<\/li>
  4. Seidel JA, Otsuka A and Kabashima K. Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations. Frontiers in Oncology. 2018<\/li>
  5. Linde N, Acebes MC, Sosa MS ve ark. Macrophages orchestrate breast cancer early dissemination and metastasis. Nature Communications, 2018.<\/li>
  6. Gardner A and Ruffell B. Dendritic Cells and Cancer Immunity. Trends Immunol. 2017<\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"

    Sevgili okur! Son y\u0131llarda t\u0131p d\u00fcnyas\u0131nda kanser tedavisi ile ilgili ge\u00e7mi\u015fe k\u0131yasla mucize olarak nitelendirebilece\u011fimiz geli\u015fmeler ya\u015fand\u0131. Hi\u00e7 ku\u015fkusuz bu<\/p>\n","protected":false},"author":61,"featured_media":872,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1,19],"tags":[],"acf":[],"views":800,"_links":{"self":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/851"}],"collection":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/users\/61"}],"replies":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/comments?post=851"}],"version-history":[{"count":6,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/851\/revisions"}],"predecessor-version":[{"id":871,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/851\/revisions\/871"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media\/872"}],"wp:attachment":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media?parent=851"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/categories?post=851"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/tags?post=851"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}