LECTURE 5
Cancers, malignant disease and the immune system
TUMOR IMMUNOLOGY
CANCER: ORIGIN AND TERMINOLOGY
Maintained balance between cell renewal and cell death.
Production of new cells is regulated - the number of particular
cells remains constant.
Cells may no longer respond to normal growth control
mechanisms and expand to produce a tumor or neoplasm.
Benign tumor is not capable of indefinite growth and does not
invade healthy surrounding tissue
Malignant tumor continues to grow and is invasive. Cancer refers
to malignant tumor.
Malignant tumors exhibit metastasis giving rise to secondary
tumors.
CLASSIFICATION OF MALIGNANT TUMORS
Carcinomas – from endodermal or ectodermal tissue (colon,
breast, prostrate and lung cancers).
Leukemias and lymphomas – tumors of hematopoietic cells of
the bone marrow. Leukemias proliferate as single cells,
lymphomas grow as tumor masses.
Sarcomas – derived from mesodermal connective tissue e.g.
Bone, fat and cartilage.
MALIGNANT TRANSFORMATION OF CELLS
Chemical, viral or radiation treatment of normal cells can alter
morphology and growth properties and produce tumors.
Chemical (DNA alkylating), physical (UV and ionizing radiation)
agents and some DNA and RNA (retroviruses) can induce
malignant transformation.
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,Such cells undergo malignant transformation and show properties
in vitro similar to cancer cells.
FUNCTIONS OF CANCER-ASSOCIATED GENES
Homeostasis is maintained by regulated process of cellular
proliferation balanced by cell death. An imbalance causes cancer
development
Oncogenes and tumor suppressor genes play an important role in
either regulating cellular proliferation or cell death.
Induction of cellular proliferation.
Inhibition of cellular proliferation.
Regulation of programmed cell death.
INDUCTION OF CANCER IS A MULTI-STEP PROCESS
Clonal evolution driven by somatic mutations.
Convert normal cell to precancerous state and finally to
cancerous state.
The precancerous and cancerous cells have high frequency in
chromosomal abnormalities and their replication leads to further
accumulation in mutations.
Demonstrated in human colon cancer.
SEQUENTIAL GENETIC ALTERATIONS LEADING TO COLON
CANCER
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, TUMORS OF THE IMMUNE SYSTEM
Lymphomas – proliferate as solid tumors within the lymphoid
tissue.
Leukemias – proliferate as single cells detectable by increased
cell numbers.
Acute leukemia – sudden and rapid progression.
Chronic leukemia – less aggressive and slow.
Major distinction is the maturity of cells involved acute leukemias
arise in less mature cells while chronic leukemias in mature cells.
TUMOR ANTIGENS
Tumor antigens are surface peptides of tumor cell proteins which
are not expressed in sufficient levels by normal cells. Hence they
are the basis for immune response to tumors
Tumor antigens are recognized by the immune system when they
are presented to T cells by MHC molecules
There are about six categories of tumor antigens:
i.Tumor-specific antigens.
ii.Antigens expressed by male germ cells.
iii.Tissue specific differential antigens.
iv.Proteins that are over-expressed by tumor cells.
v.Peptides with abnormal post-translational modifications.
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Cancers, malignant disease and the immune system
TUMOR IMMUNOLOGY
CANCER: ORIGIN AND TERMINOLOGY
Maintained balance between cell renewal and cell death.
Production of new cells is regulated - the number of particular
cells remains constant.
Cells may no longer respond to normal growth control
mechanisms and expand to produce a tumor or neoplasm.
Benign tumor is not capable of indefinite growth and does not
invade healthy surrounding tissue
Malignant tumor continues to grow and is invasive. Cancer refers
to malignant tumor.
Malignant tumors exhibit metastasis giving rise to secondary
tumors.
CLASSIFICATION OF MALIGNANT TUMORS
Carcinomas – from endodermal or ectodermal tissue (colon,
breast, prostrate and lung cancers).
Leukemias and lymphomas – tumors of hematopoietic cells of
the bone marrow. Leukemias proliferate as single cells,
lymphomas grow as tumor masses.
Sarcomas – derived from mesodermal connective tissue e.g.
Bone, fat and cartilage.
MALIGNANT TRANSFORMATION OF CELLS
Chemical, viral or radiation treatment of normal cells can alter
morphology and growth properties and produce tumors.
Chemical (DNA alkylating), physical (UV and ionizing radiation)
agents and some DNA and RNA (retroviruses) can induce
malignant transformation.
87
,Such cells undergo malignant transformation and show properties
in vitro similar to cancer cells.
FUNCTIONS OF CANCER-ASSOCIATED GENES
Homeostasis is maintained by regulated process of cellular
proliferation balanced by cell death. An imbalance causes cancer
development
Oncogenes and tumor suppressor genes play an important role in
either regulating cellular proliferation or cell death.
Induction of cellular proliferation.
Inhibition of cellular proliferation.
Regulation of programmed cell death.
INDUCTION OF CANCER IS A MULTI-STEP PROCESS
Clonal evolution driven by somatic mutations.
Convert normal cell to precancerous state and finally to
cancerous state.
The precancerous and cancerous cells have high frequency in
chromosomal abnormalities and their replication leads to further
accumulation in mutations.
Demonstrated in human colon cancer.
SEQUENTIAL GENETIC ALTERATIONS LEADING TO COLON
CANCER
88
, TUMORS OF THE IMMUNE SYSTEM
Lymphomas – proliferate as solid tumors within the lymphoid
tissue.
Leukemias – proliferate as single cells detectable by increased
cell numbers.
Acute leukemia – sudden and rapid progression.
Chronic leukemia – less aggressive and slow.
Major distinction is the maturity of cells involved acute leukemias
arise in less mature cells while chronic leukemias in mature cells.
TUMOR ANTIGENS
Tumor antigens are surface peptides of tumor cell proteins which
are not expressed in sufficient levels by normal cells. Hence they
are the basis for immune response to tumors
Tumor antigens are recognized by the immune system when they
are presented to T cells by MHC molecules
There are about six categories of tumor antigens:
i.Tumor-specific antigens.
ii.Antigens expressed by male germ cells.
iii.Tissue specific differential antigens.
iv.Proteins that are over-expressed by tumor cells.
v.Peptides with abnormal post-translational modifications.
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