Ziad Elnasser, MD, Ph.D
Two main strands of tumour immunology.Genetics.Pathogens.Tumors of lymphoid cells.Tumor immunotherapy.
From single lymphocyte or plasma cell.Monoclonality.The biology of the originating cell.ALL and pre-B cell, myeloma from plasma.Oncogene activation by chromosomal
translocations, and effects of pathogens.
Oncogenesis Chromosomal translocations:
Repairing of translocations fails. Some have +ve effect on cell survival. Lymphoma and c-myc (8)bcl-2 (18) to 14 regulates. Radiation exposure.
Pathogens Herpesviruses, retroviruses, EBV (immortalization),
block proteosome, Burkitt’s lymphoma (Polyclonal B cell activation), translocation myc activation.
HHV-8 and KS. Helicobacter pylori, Lymphoma HTLV-1 and T cell lymphoma, Tax activation, as IL-2
Diagnosis of Lymphoid Malignancy
Appearance of abnormal cells.Flow cytometry, AML from ALL.Monoclonality and MM, B-cell lymphoma.
Immunity to Tumors Hope to use immune therapy against. Tumor Antigens:
Developmental proteins, CEA and GIT tumors, weak Ags. Screening use.
Lineage-specific proteins: Tyrosinase, and Melanoma cells weak Ags..
Viral proteins: EBV, HPV highly antigenic, effect of vaccines HBV, HPV.
Proteins produced through translocation: Bcr-Abl fusion protein product of bcr/abl translocation.
Evidence for Tumor Immunity: Occurance in immunocompromised pts. Tumor recognition by TIL. TNF
Evasion of the Immune Response by Tumors
No alert signal through the innate, NK?Low expression of MHC, alternative NK.Share same self Ags.Low levels of costimulatory molecules.Viruses might inhibit proteosome
processing of antigen.
Immunotherapy Passive cancer immunotherapy:
Anti-CD20, and Iodine conjugated, used also for spread detection of lymphoma.
Trastuzmab (Herceptin): against HER-2 (Human Epidermal Growth factor) receptor in Breast cancer, induces ADCC, down by 30%.
Active cancer immunotherapy: To overcome the anergy mediated by T cells. Anergy develops when tumor cell presents Ag to Th
cell without costimulatory molecules. CpG and Imiquimod use on TLR-9 and TLR-7. Use of IL-2, could cause the capillary leak syndrome. INF-α, INF-β, and effect on MHC.