Respon Imun Terhadap KankerD.H. Setya Palupi

DefinisiAda pengaturan keseimbangan antara pembaharuan sel dan kematian selTumor/ Neoplasma = perkembangan sel yang tidak terkontrolTumor yang berkembang dan menyebar kanker

JinakNon invasifGanasInvasif dan metastasis

Tumor ganastumor ber-metastase dan berkembangbiaktumor sekunderKlasifikasi tumor ganas/ kanker berdasar asal jaringan embrio asal, yi:Karsinoma (jar endodermal/ektodermal kulit dan lapisan epitel organ internal dan kelenjar)Kanker sel darah/ hematopoietic cells leukimia dan limfomaSarkoma (jar ikatjar mesodermal tulang, lemak dan tulang rawan)

How do cells become transformed into malignant cells?RadiationCarcinogensVirusesexpression of oncogenes (aberrant versions of proto-oncogenes)

Ada 2 fase :Inisiasiperubahan dalam genomPromosipembelahan sel >>

Mutasi

Tipe pengaturan genProto-onkogenik menginduksi proliferasi dalam beberapa cara.Tumor suppressors menekan proliferasi selRegulasi apoptosis

Defects in any of these can lead to uncontrolled cell growth

Mutasi gen yang terakumulasi dalam sel akan membuat secara bertahap di konversikan menjadi sel ganas.

Translokasi terjadi pada kanker yg spesifik

Sel tumor berbeda dari sel normal => dikenal sbg non-self / foreignimmune responses fail to prevent tumor growth external activation of the immune system

Ada 2 tipe :tumor-specific transplantation antigens (TSTAs) unik utk tumor, tidak terjadi pd sel normalhasil mutasi pd sel tumor yang menghasilkan perubahan protein selularMHC kelas Iinduksi respon imun dimediasi sel oleh CTL spesiifik tumor.tumor-associated transplantation antigens (TATAs). Tidak unik untuk sel tumorHasil ekspresi protein pd sel normal selama pembentukan janin (sistem imun msh belum matang dan tdk dapat merespon)

mutations abnormal expression oncogenic viruses oncofetal antigens altered surface modifications tissue specific differentiation antigens

innate immune responses NK cells macrophages adaptive immune responses T cells antibodies

Anti-tumor antibody can block T cell responses (enhance tumor growth)Tumors can modulate antigens Ag modulation (Abs bind to Ag on leukemic cells, induce capping, endocytosis of Ag, shedding of Ag-Ab complexes)Tumors can reduce MHC Class I expression (selection; escape CTL recognition)Tumors can reduce second signal expression (no B7 -> clonal anergy)

Strategi ImunoterapiMake cells more immunogenic better CTL activation vaccine made up of cells?Enhancement of APC activity can modulate tumor immunity BCG attenuated Mycobacterium bovis mouse dendritic cells incubated with GM-CSF and tumor fragments, then into animal, activate anti-tumor Th and CTLs

Immunotherapy stimulation of immune responsevaccination with tumor cellscostimulators and cytokinesblock inhibitory pathwaysnonspecific stimulation of the immune system

Tumor vaccines

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Systemic cytokine therapy

Immunotherapy passive immunotherapy adoptive cellular therapy graft-versus-leukemia antibodies

Monoclonal antibodies

Figure 14-17

Peransistem imun tubuhthd pertumbuhan tumor chronic inflammation as risk factor for cancer Helicobacter pylori (gastric cancer) hepatitis B and C (hepatocellular carcinoma)

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