Tumor immunity | Cancer | Neoplasms

Tumor Immunity

basics
Dr.T.V.Rao MD

Dr.T.V.Rao MD

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Tumor
• Cells that continue to replicate, f Cells that continue to replicate, fail to differentiate into specialized cells, and become immortal.

1. Malignant: A tumor that grows

indefinitely and spreads (metastasis)--also called cancer: kills host

2. Benign: A tumor
that is not capable of
metastasis: does not kill host

muscle, nerve, bone, blood

Types of Cancer
• Carcinoma: arising from epithelial tissue, such as glands,
breast, skin, and linings of the urogenital, digestive, and respiratory systems (89.3% of all cancers)

• Sarcoma: solid tumors of muscles, bone, and cartilage that
arise from the embryological mesoderm (1.9% of all cancers)

• Leukemia: disease of bone marrow causing excessive
production of leukocytes (3.4% of all cancers)

• Lymphoma, Myeloma: diseases of the lymph nodes
and spleen that cause excessive production of lymphocytes (5.4% of cancers)
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Etiology of Cancer
1. Genetic factors: mutations, translocation, amplifications 2. Environmental factors: UV, chemicals, viral infections • Conversion of proto-oncogenes (potential for cell transformation) to oncogenes (cell transformation) alteration in tumor suppressor genes
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Tumour Antigens
• When a cell undergoes malignant transformation it acquires new surface antigens and may loose some normal antigens • A malignant tumour antigenically different from normal tissues of the host it is considered as an allograft and expected to induce immune response.
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Tumour Antigens
• Antigens that are present in the tumour cells but absent in the corresponding normal cell of the host are known as tumour antigens • Two types – tumour specific and tumour associated antigens
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Tumour specific antigens
• These are antigens present on the membrances of the malignant cells and induce an immune response when the tumour is transplanted in syngenic animals

• TATA Tumour associated transplantation
antigens • TSTA Tumour specific transplantation antigens
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Tumour associated antigens
• These are foetal antigens that are present in embryonic and malignant cells but not in the adult normal cells. • Examples – • Alpha fetoproteins in hepatoma and carcinoembronic antigen in the colonic cancer
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Evidence to tumour Immunity
• High frequency in cancers in immunosuppressed patients Papilloma virus driven cervical cancer • AIDS lymph reticular malignancies • Immunosuppressive therapy
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Tumor killing
Non-specific: NK cells, gd T cells (NKG2D), macrophages, NK T cells
Antigen-specific: Antibody (ADCC, opsinization); T cells (cytokines, Fas-L, perforin/granzyme)
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Immune Response in Malignancy

• T cell mediated immunity • Lymhokines helps in destruction of tumour cells • Humoral response is beneficial
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Virally-induced Cancers
DNA viruses: papova (papilloma, SV40),

hepatitis, EBV
RNA viruses: retroviruses---> Human Tlymphotropic viruses (HTLV-I and HTLV-II) cause T cell leukemia

Hepatitis C viral Infection
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Immunological surveillance
• In 1970 Burnet proposed that malignant cells arise by somatic mutation and the immune system keeps a constant vigilance on these cells and destroy them • Fast rate of growth of malignant cells
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Evidence for Tumor Immunity
• Spontaneous regression: melanoma, lymphoma

• Regression of metastases after removal of primary tumor: pulmonary metastases from renal carcinoma • Infiltration of tumors by lymphocytes and macrophages: melanoma and breast cancer

• Higher incidence of cancer after immunosuppression, immunodeficiency (AIDS, neonates), aging, etc.
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Immunotherapy of Cancer
• Non specific active immune therapy employs BCG • BCG evokes tumour immunity enhancing macrophage cytotoxicity • Levamisole
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Specific Immunotherapy
• Monoclonal antibodies to tumour antigens • Lymhokines activated killer cells obtained by treatment of natural killer cells with interleukin used in renal carcinoma
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Summary
• Both genetic and environmental factors are involved in tumor formation • Immune system plays a surveillance role in controlling the development of cancer, however, it also induces epigenetic changes in tumors that result in cancer (immune editing)
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Summary ( Contd)
• Altered expression of antigens by tumors (mutation, viral antigens, cryptic epitopes), expression of costimulatory molecules in tumors, or cross-presentation of tumor antigens by APC results in the immune recognition of tumor cells
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• The Programme Created by Dr.T.V.Rao MD for Medical Students in the Developing World

• Email • doctortvrao@gmail.com

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