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TUMOR IMMUNOLOGY

TUMOR IMMUNOLOGY. Jan Żeromski 2011/2012. EVIDENCE FOR ANTI-TUMOR IMMUNOLOGICAL REACTIVITY. Lymphoid cell infiltrates and proliferative reaction in regional lymph nodes correlate with favourable prognosis in some tumors,

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TUMOR IMMUNOLOGY

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  1. TUMOR IMMUNOLOGY Jan Żeromski 2011/2012

  2. EVIDENCE FOR ANTI-TUMOR IMMUNOLOGICAL REACTIVITY • Lymphoid cell infiltrates and proliferative reaction in regional lymph nodes correlate with favourable prognosis in some tumors, • Transplants of experimental tumors are rejected in animals previously exposed to the same tumor,

  3. EVIDENCE FOR ANTI-TUMOR IMMUNOLOGICAL REACTIVITY-2 • This resistance may be transfered to another animal by means of lymphocytes of animal previously harboring or exposed to this tumor, • Individuals with immunodeficiencies show higher frequencies of some tumor types

  4. IMMUNOLOGICAL SURVEILLANCE • Definitionprevention of development of the majority of tumors by early destruction of atypic cells by the immune system of the host. • Evidencespontaneous regression of cancer, higher incidence of tumors in early childhood and in elderly people, autopsy findings.

  5. TUMOR ANTIGENS • Tumor specific antigens (TSA) : expressed only on tumor cells and not on normal ones • Tumor associated antigens (TAA)- may be expressed in variable amounts also on normal cells

  6. TUMOR ANTIGENS-2 In terms of origin the following TAA are distinguished: • Ag of spontaneous tumors of unknown etiology • Ag of tumors induced by oncogenic viruses • Ag carcino-embryonic (oncofetal ones) • Ag of tumors induced by chemicals and/or radiation

  7. TYPES OF TUMOR ANTIGENS RECOGNISED BY T CELLS

  8. VIRUSES AND HUMAN TUMORS • Primary liver cancer: HBV, HCV • Cervical cancer: HPV 16, 18 and other • Burkitt lymphoma and other lymphomas: EBV • Nasopharyngeal carcinoma: EBV: HTLV-1 • Adult T cell leukaemia: (HTLV-1) • Kaposi sarcoma: herpes virus-8 (KSHV)

  9. ONCO-FETAL ANTIGENS • Features: not expressed in healthy people in postnatal life but may abundant in fetal period. They are encoded in geno • Their expression is the result of derepression of particular gene.

  10. ONCO-FETAL ANTIGENS-2 • Carcinoembryonic antigen(CEA): cell membrane glycoprotein (200 kDa) of many human cancers • -fetoprotein (fetal albumin) major fetal serum protein. Present in cells of primary hepatic carcinoma and in malignant germinal teratomas • PSA – prostate specific antigen

  11. IMMUNOLOGICAL FACTORS OF ANTI-TUMOR RESPONSE • Antibodies • Cytotoxic T lymphocytes - CTL (CD8+) • Cytokines with cytotoxic properties (TNF-alfa, LT) • Immunoregulatory cytokines (IFN-gamma, IL-2, IL-12, IL-18) • NK cells, NKT cells, gamma/delta T cells • Macrophages, granulocytes - ADCC

  12. TUMOR ESCAPE MECHANISMS • Tumor’s progression and growth are faster than the generation of the immune response („sneaking through” mechanism) • Tumor and its microenvironment inactivate most of the host defense mechanisms

  13. HLA I-

  14. CD44 v6

  15. TUMOR CELL COUNTER ATTACK

  16. MALIGNANT PLEURAL EFFUSIONS SURFACE EXPRESSION OF Fas AND FasL ON TUMOR CELLS

  17. TUMOR EVASION OF HOST IMMUNE RESPONSE

  18. IMMUNOTHERAPY OF CANCER

  19. TUMOR IMMUNOTHERAPY- POSSIBILITIES • Monoclonal antibodies • Sensitized T (CD8+) cells • LAK cells (lymphokine activated killers) • Cytokines or their genes (IL-2, IL-12, IFN-alfa etc.)

  20. TUMOR IMMUNOTHERAPY- POSSIBILITIES -2 • NK cells • Co-stimulatory molecules or their genes inserted into tumor cells • Dendritic cells loaded with tumor peptides • Nonspecific immunotherapy (BCG)

  21. Monoclonal Antibodies used in Cancer Therapy • Campath 1H [CD52] - CLL • Rituximab [CD20] - as above • Epratuzumab [CD22] - as above • IDEC-152 [CD23] - as above • Cetuximab [EGFR] - colon, HNC • MDX-447 [EGFR i CD64] - as above • Gefitinib [EGFR-TK] - prostate, lung cancer • Herceptin [EGFR] - mammary cancer

  22. Gene Gun

  23. Tumor microenvironment.Evaluation of fine needle aspiration biopsy by means of DNA microarray

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