Tumor Immunity

basics
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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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