Tumor Immunology

Tumor Immunology     evidence for immune reactivity against tumor changes in cellular characteristics due to malignancy tumor and host components which affect tumor progression use of tumor antigens in diagnosis and immunotherapy 1 Evidence for immunosurveillance Infiltration of malignant tissue 2 Association between immunodeficiency and cancer cause of immunodeficiency  malignancy lymphomas lymphoma, cervical cancer, liver cancer, skin cancer, Kaposi’s sarcoma. primary (inherited) immunodeficiency secondary (acquired) immunodeficiency    malaria autoimmunity Burkitt’s lymphoma lymphoma 3 Tumors stimulate an immune response Animals can be immunized against tumors  Immunity is transferable from immune to naïve animals  Tumor specific antibodies and cell have been detected in humans with some malignancies  4 Neo-antigens of immunologic significance on tumor cells  Oncofetal/differentiation antigens    Alpha-feto-protein (AFP) Cracino-embryonic antigen (CEA) CALLA (common acute lymphoblastic leukemia antigen: CD10)  Tumor-associated transplantation antigens   Virus associated shared antigens Tumor specific transplantation antigen 5 Alpha fetoprotein: clinical use AFP increases in testicular and liver cancers  Aids in diagnosis and staging  Patient management  Detection of tumors 6 Alpha fetoprotein: clinical use 7 Alpha fetoprotein: concentrations Normal concentration: <20 ng/ml  Abnormal concentrations   100-350 possible hepatoma  350-500 probable hepatoma  500-1000 likely hepatoma  >1000 HEPATOMA 8 Carcinoembryonic antigen: clinical use     Adjunct in diagnosis Staging and prognosis Monitoring response to therapy Detection of tumor recurrence 9 Carcinoembryonic antigen: clinical use 10 Carcinoembryonic antigen: clinical use CEA as a diagnostic adjunct   Symptomatic patient Elevated value 5-10 times the upper limit Normal value <10ng/ml 11 Tumor associated transplantation antigens: shared Ag on virally induced tumors inject an oncogenic virus (SV40) 2 weeks remove tumors A& B isolate tumor cells immunize with irradiated tumor A cells 2 weeks challenge with live tumor A 2 weeks no tumor challenge with live tumor B 2 weeks no tumor 2 weeks 12 Tumor associated transplantation antigens: unique Ag on chemically induced tumors inject carcinogen (MCA) 2 weeks remove isolate tumors tumor cells A& B immunize with irradiated tumor A cells 2 weeks challenge with live tumor A 2 weeks no tumor challenge with live tumor B 2 weeks tumor 2 weeks 13 Immunity against tumor All components, specific and nonspecific, humoral and cellular affect tumor progression and growth 14 Escape from immunosurveillance Lack of Neo-antigens 15 Escape from immunosurveillance Lack of co-stimulatory molecules 16 Escape from immunosurveillance Lack of class I MHC 17 Escape from immunosurveillance Tumors secrete Immunosuppressive molecules 18 Escape from immunosurveillance Tumors shed their neo-antigens 19 Use of tumor associated antigens  Raise   monoclonal antibodies Use antibodies for diagnosis Use antibodies for therapy  Stimulate   the in vivo specific response  Specific active treatment Specific passive treatment Adjuvant therapy to augment specific immunity 20 Use of tumor associated antigens monoclonal antibodies toxin tumor radioisotope drug Enzyme prodrug 21 Monoclonal antibodies: use as a diagnostic tool 22 Immunotherapy of tumors active immunotherapy specific nonspecific killed tumor cells, purified or recombinant Ag BCG, Propionibacterium acne, levamisole, etc. passive immunotherapy non-specific specific LAK cells, cytokines antibodies alone or conjugated with other agent, activated T cells 23 Non-specific immunotherapy bacterial products BCG, P. acnes, muramyl dipeptide activate macrophages and NK cells (via cytokines) synthetic molecules pyran, poly I:C interferon production cytokines IFN- , IFN-, IFN- , IL-2, TNF-  activate macrophages and NK cells 24 Cytokine immunotherapy IFN-, - IFN- remission of hairy cell leukemia, weak effect on carcinomas remission of ovarian carcinoma remission in renal cell carcinoma and melanoma reduction in malignant ascites increased expression of class-I MHC, possible anti tumor effect increased expression of class-I MHC, Tc and NK cell activation T cell proliferation and activation, NK cell activation IL-2 TNF-  macrophage and lymphocyte activation 25 Genetic approaches to cancer treatment  Transfection with genes  Cytokines  Class I MHC  Co-stimulatory molecules 26