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Tumor immunology
The document discusses tumor immunology, focusing on the immune response to tumors, the identification of tumor antigens, and mechanisms of cancer immunotherapy. It explains the roles of proto-oncogenes in cancer development and highlights strategies to enhance anti-tumor immunity through various cellular and cytokine therapies. The conclusion emphasizes the distinct characteristics of tumor cells compared to normal cells and the progress in identifying tumor-associated antigens.
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Tumor immunology
- 1. Sahyadri science college,Shivamogga SeminarTopic On TUMOUR IMMUNOLOGY Submitted by: MAHANTHESHKUMAR G T 1st M.Sc Biotechnology Dept of biotechnology Sahyadri science college, Shivamogga.
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- 3. • Tumor immunologyis mainly to study the immunogenicity of tumor and the mechanism of immune response to tumor, to demonstrate the relationship between the status of immune system and the generation, development of tumor, to explore the method of tumor diagnosis, therapy and prevention. . Immunosurveillance IntroductionIntroduction
- 4. CANCER: ORIGIN AND TERMINOLOGY •In most organs and tissues of a mature animal, a balance is usually maintained between cell renewal and cell death. The various types of mature cells in the body have a given life span; as these cells die, new cells are generated by the proliferation and differentiation of various types of stem cells
- 5. Malignant Transformation ofCells Induction of malignant transformation with chemical or Physical carcinogens appears to involve multiple steps and at least two distinct phases: initiation and promotion. Initiation involves changes in the genome but does not, in itself, lead to malignant transformation. After initiation, promoters stimulate cell division and lead to malignant transformation.
- 6. ONCOGENES AND CANCERINDUCTION In 1971, Howard Temin suggested that oncogenes might not be unique to transforming viruses but might also be found in normal cells; indeed, he proposed that a virus might acquire oncogenes from the genome of an infected cell He called these cellular genes proto- oncogenes, or cellular oncogenes (c- onc), to distinguish them from their viral counterparts (v-onc) In the mid-1970s, J. M. Bishop and H. E. Varmus identified a DNA sequence in normal chicken cells that is homologous to v-src from Rous sarcoma virus. This cellular oncogene was designated c-src. Since these early discoveries, numerous cellular oncogenes have been identified.
- 7. Proto-Oncogenes Can BeConverted to Oncogenes In 1972, R. J. Huebner and G. J. Todaro suggested that mutations or genetic rearrangements of proto-oncogenes by car-cinogens or viruses might alter the normally regulated function of these genes, converting them into potent cancer-causing oncogenes. some malignantly transformed cells contain multiple copies of cellular oncogenes, resulting in increased production of onco-gene products.
- 8. Tumors of theImmune System Tumors of the immune system are classified as lymphomas or leukemias. Lymphomas proliferate as solid tumors within a lymphoid tissue such as the bone marrow, lymph nodes, or thymus; they include Hodgkin’s and non-Hodgkin’s lym-phomas. Leukemias tend to proliferate as single cells and are detected by increased cell numbers in the blood or lymph. Leukemia can develop in lymphoid or myeloid lineages
- 9. TUMOR ANTIGENS The subdisciplineof tumor immunology involves the study of antigens on tumor cells and the immune response to these antigens. Two types of tumor antigens have been identified on tumor cells: tumor-specific transplantation antigens (TSTAs)&tumor-associated transplantation antigens (TATAs) Antigens encoded by genes exclusively expressed by tumors Antigens encoded by variant forms of normal genes that have been altered by mutation
- 10. SOME ANTIGENS ARETUMOR-SPECIFIC Tumor-specific antigens have been identified on tumors induced with chemical or physical carcinogens and on some virally induced tumors. Demonstrating the presence of tumor- specific antigens on spontaneously occurring tumors is particularly difficult because the immune response to such tumors eliminates all of the tumor cells bearing sufficient numbers of the antigens and in this way selects for cells bear-ing low levels of the antigens
- 11. Tumor Antigens MayBe Induced by Viruses In contrast to chemically induced tumors, virally induced tumors express tumor antigens shared by all tumors induced by the same virus. For example, when syngeneic mice are injected with killed cells from a particular polyoma-induced tumor, the recipients are protected against subsequent challenge with live cells from any polyoma-induced tumors.
- 12. SCHIMATIC REPRESENTATION OF THEANTI –TUMOR IMMUNE RESPONSE Following the discovery that antibodies could be produced to tumor-specific antigens, attempts were made to protect animals against tumor growth by active immunization with tumor antigens or by passive immunization with antitumor antibodies. Much to the surprise of the researchers, these immunizations did not protect against tumor growth; in many cases, they actually enhanced growth of the tumor
- 13. Antibodies Can ModulateTumor Antigens Certain tumor-specific antigens have been observed to disappear from the surface of tumor cells in the presence of serum antibody and then to reappear after the antibody is no longer present This phenomenon, called antigenic modulation, is readily observed when leukemic T cells are injected into mice previously immunized with a leukemic T- cell anti-gen (TL antigen). These mice develop high titers of anti-TL antibody, which binds to the TL antigen on the leukemic cells and induces capping, endocytosis , and/or shedding of the antigen-antibody complex.
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- 15. ENHANCEMENT OF APCACTIVITY CAN MODULATE TUMOR IMMUNITY Use of transfected tumor cells for cancer im-munotherapy. (a) Tumor cells transfected with the B7 gene express the co-stimulatory B7 molecule, enabling them to provide both acti-vating signal (1) and co-stimulatory signal (2) to CTL-Ps. As a result of the combined signals, the CTL-Ps differentiate into effector CTLs, which can mediate tumor destruction. In effect, the transfected tu-mor cell acts as an antigen-presenting cell. (b) Transfection of tumor cells with the gene encoding GM-CSF allows the tumor cells to se-crete high levels of GM-CSF. This cytokine will activate dendritic cells in the vicinity of the tumor, enabling the dendritic cells to present tu-mor antigens to both TH cells and CTL-Ps.
- 16. CYTOKINE THERAPY CANAUGMENT IMMUNE RESPONSES TO TUMORS The isolation and cloning of the various cytokine genes has facilitated their large-scale production. A variety of experimental and clinical approaches have been developed to use recombinant cytokines, either singly or in combination, to augment the immune response against cancer. Among the cytokines that have been evaluated in cancer immunotherapy are IFN- , , and ; IL-1, IL-2, IL-4, IL-5, and IL-12; GM-CSF; and TNF. Although these trials have produced occasional encouraging results, many obstacles remain to the successful use of this type of cancer immunotherapy.
- 17. IN VITRO–ACTIVATED LAKAND TIL CELLS Photomicrographs of cultured normal melanocytes (top) and cultured cancerous melanoma cells (bottom) in the presence (left) and absence (right) of tumor necrosis factor (TNF- ). Note that, in the presence of TNF- , the cancer cells stop proliferating whereas TNF- has no inhibitory effect on proliferation of the normal cells. Animal studies have shown that lymphocytes can be activated against tumor antigens in vitro by culturing them with x-irradiated tumor cells in the presence of IL-2 and added tumor antigens. These activated lymphocytes mediate more effective tumor destruction than untreated lymphocytes when they are re injected into the original tumor-bearing animal.
- 18. CONCLUSION Tumor cellsdiffer from normal cells in numerous ways. In particular, changes in the regulation of growth of tumor cells allow them to proliferate indefinitely, then invade the underlying tissue, and eventually metastasize to other tissues. Normal cells can be transformed in vitro by chemical and physical carcinogens and by transforming viruses. Transformed cells exhibit altered growth properties and are sometimes capable of inducing cancer when they are injected into animals. The use of a variety of genetic, biochemical, and immunological approaches has allowed the identification of several tumor-associated antigens In many cases the antigen is expressed on more than one type of tumor.
- 19. Reference: Kuby byimmunology 6th edition Paradoll .D.M 1996 cancer vaccines a road map for the next decade.curr.opin.immunology http://www.oncalink.upenn.edu/ http://www.cancer.org/index_4up.html •