tumor immunology.pptx

tumor immunology

1. Tumor immunology Dr / Eman Ahmed Abd-Arahman Lecturer of medical microbiology and immunology

2. Tumor immunology Immune surveillance : Tumor cells become antigenically different from normal cells and so they can be recognized by the immune system and destroyed.

3. Tumor antigens 1- Tumor antigens encoded by genome of oncogenic viruses : Def : Cells infected by oncogenic viruses display new antigens Examples : - Epstein Barr virus → Burkitt's lymphoma Human papilloma virus → cervical cancers

4. Tumor antigens 2- Oncofetal antigens : Def : These antigens are present during normal fetal development but are lost during adult life . However, these antigens may reappear in cancer cells . Examples : alpha feto protein ( AFP ) → hepatic carcinoma carcino-embryonic antigen ( CEA ) → cancer intestine

5. Tumor antigens 3- Products of mutated self genes , also called tumor specific transplantation antigens ( TSTAs) : Def : Mutation of the self host genes mainly due to chemical carcinogens & radiation . The result antigens are extremely diverse because the carcinogens can randomly mutagenize any other host cells Examples : random mutations → random tumors

6. Tumor antigens 4-Tissue-specific differentiation antigens: it is normal differentiation antigens specific for the tissue from which the tumor aroused, e.g. prostatic specific antigens (PSA) are detected in prostatic tumour which are also released into the serum and can be measured as a screening test for prostatic cancer.

7. Tumor antigens 5- Over-expressed and abnormally expressed cellular proteins: Tumor antigens· may be normal cellular proteins that are abnormally expressed in tumor cells and elicit immune response e.g. melanoma antigen genes (MAGE). These antigens are encoded for by families of genes that are normally silent in all normal tissues except human testis. These genes code for proteins found on the surface of a large number of tumors, including melanomas, bladder, breast, skin and prostatic cancer.

8. Immune response to tumor antigens TH cell is the main co-organizer for the immune response via production of IL2 & IFN so :- 1- Macrophages : when activate can kill tumor cells by : a- Cell contact cytotoxicity b- Antibody dependent cellular cytotoxicity (ADCC)

9. 2- NK cells : cause spontaneous lysis of tumors , IFN-y activated NK cells are more efficient ( lymphokine activated killer LAK ) They can also kill tumor cells by ADCC. Immune response to tumor antigens

10. Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)

11. 3- T cells : play the major role in defense against tumor growth a- CTLs killing of tumor cells is the principle mechanism of tumor immunity . CTLs recognize tumor antigens in association with MHC-I and kill them b- TH activated by tumor antigens release cytokines as IFN-y . These help differentiation of CTLs and increase the expression of MHC-I on tumor cells to be more sensitive to lysis by CTLs . They also activate NK cells and macrophages Immune response to tumor antigens

12. Immune response to tumor antigens 4- Humoral mechanisms : has minor role by : a- Complement fixation & activation b- Opsonization c- ADCC

13. Evasion of immune response by tumors 1- Tumor stop expressing the antigens that are the targets of immune attack " antigen loss variants " and they are rapidly growing tumors 2- Reduced levels or absence of MHC-I , so they cannot be recognized by CTLs 3- Defects in antigen processing and presentation due to lack of co-stimulator signals e.g.B7

14. Evasion of immune response by tumors 4- Blocking antibodies : these are non complement fixing anti tumor antibodies that bind to antigen sites on surface of tumor and make them inaccessible to immunity 5- Tumors produce immunosuppressive factors 6- Immune suppression of host as in transplant patients → ↑ incidence of malignancy

15. Evasion of immune response by tumors 7- Tumor antigens induce immune tolerance 8- Treg suppress T cell responses to tumors so number of Treg is increased in cancer patients 9- Soluble antigens shed by the tumor acting as free antigens that mask the tumor antigen recognition by T cells 10- Antigens on surface of tumors may be masked by sialic acid

16. Cancer immunotherapy Reduction of tumor mass by surgery , irradiation or chemotherapy is very essential before immunotherapy: 1) Specific Active immunotherapy : Many vaccines are under trails , for example : Viral vaccines against oncogenic viruses will increase incidence of tumor as HPV vaccine will prevent occurrence of cervical carcinoma

17. Cancer immunotherapy 2) Specific Passive Humoral immunotherapy : a- Magic bullet therapy : use of monoclonal antibodies directed against tumor antigens and linked to cytotoxic drugs,radioactive isotopes or TNF , it carry tumor destroying agents specifically and directed to tumor cells only b- Monoclonal An against Her2/neu in breast cancer

18. Cancer immunotherapy 3) Specific Passive Cellular immunotherapy : -LAK therapy : re-infusion of patients own peripheral lymphocytes after their activation in vitro by IL-2 or IFN-y . Better results occurs when IL-2 is given to patient directly but it leads to many side effects

19. Cancer immunotherapy 4) Non Specific immunostimulation : a-Use of certain bacterial products as BCG vaccine which stimulates CMI non-specifically , activating macrophages and NK cells so used in ttt of superficial bladder cancer. b-Cytokine therapy : systemic administration of IL-2 , IFN and others is under trails but it has toxic side effects

20. Tumor markers Def : Enzymes or tumor products secreted in blood and used to confirm the diagnosis of certain tumors and to monitor the response to therapy: Examples : 1- Alpha feto protein ( AFP ) → hepatic carcinoma 2- Carcino -embryonic antigens ( CEA ) → GIT cancer 3- Human chorionic gonadotrophin ( HCG ) → choriocarcinoma 4- Prostatic specific antigen ( PSA ) → prostatic tumor 5- Bence-Jones proteins in urine → multiple myeloma 6- CA 15-3 → breast cancer 7- CA 19-9 → colon caner 8- CA 125 → ovarian cancer