› the study of the antigens associated with tumors, the immune

response to tumors, the tumor’s effect on the host’s immune status,

and the use of the immune system to help eradicate the tumor.
› Proto-oncogenes-genes that normally regulate the initiation and
execution of normal cells
› Oncogenes-the mutant forms of proto-oncogenes that contribute to
various tumor types or malignant transformation
› Tumor suppressor genes-removes growth-inhibitory signals that can
cause tumors
 Tumors
 are composed of cells that possess many of the attributes of the
normal cells from which they arose but have accelerated or
dysregulated growth
 BENIGN TUMORS- not immortal and a tumor does not invade
surrounding tissue and normal body function is largely preserved
 MALIGNANT TUMOR-immortal, progressively invasive,
CANCEROUS, can invade surrounding tissues and greatly disrupt
normal body function
 METASTASIS-moves through the blood or lymph to new
sites, small clumps of cells that break off and spread where
they continue to grow
 when the malignant cells travel through the body, causing
new foci of malignancy until body function is so disrupted
that death occurs.
 Malignant cells typically differ visually from normal cells, are
metabolically more active to support their growth, and express
different genes or different levels of gene products as compared to
normal cells
 arise from the endodermal
or ectodermal ephithelial
tissue
 cancers or malignancies that
begin in the epithelial cells,
which are the cells that make
up the skin, and the tissues
that line various internal
organs and structures. Some
of the most common
carcinomas affect the breast,
lung, prostate, and colon.
 a malignant tumor, a type of
cancer that arises from
transformed cells of
mesenchymal (connective
tissue) origin. Connective
tissue is a broad term that
includes bone, cartilage, fat,
vascular, or hematopoietic
tissues, and sarcomas can
arise in any of these types of
tissues.
 malignant tumors of
hematopoietic cells of the
bone marrow
 Leukemia-involves mainly
WBCs
 Lymphoma-involves
lymphocytes
 The conversion of a normal cell to a malignant cell is
typically a process, not an event.
1. Induction phase
 cells are exposed to a variety of environmental insults, including
chemical carcinogens, oncogenic viruses, and radiation (ionizing
and ultraviolet). Cancer may only develop as the result of multiple
mutations caused by these insults, and it more readily develops in
cells genetically predisposed to these mutations.
 take months to years, cells exhibit dysplasia or abnormal growth
that is not yet considered neoplasia, or consistent with a tumor.
2. In situ phase of cancer
 when neoplastic cells have formed but are confined to the tissue of
origin
3. Invasion phase
 cells are malignant and tries to invade normal tissues
4. Dissemination phase
 tumor cells travel throughout the body, usually via the blood and
lymphatics
 Tumors are also classified by the TNM system by the size of
the primary tumor (T), the involvement of adjacent lymph
nodes (N), and the detection of metastasis (M)
 Immunosurveillance by the immune system to eradicate
cancer cells as they form has long been postulated. There
is increased incidence of tumors in those with deficient
immune systems such as the elderly and in
immunosuppressed individuals, but this is not proof of the
existence of immunosurveillance.
 Tumor-specific antigens
 not found on normal somatic cells (unique to tumor cells) but
result from mutations of genes
 represent fragments of novel peptides (small proteins) that are
presented at the cell surface bound to the major histocompatibility
complex class I molecules. In that form they are recognized by T
lymphocytes (T cells) and eliminated.
 Tumor-associated antigens (TAA)-antigens present in the
tumor tissue in higher amounts than in normal tissue
 Oncofetal antigens
 expressed on tumors and on normal fetal cells
 Example: alpha - 1 - fetoprotein (AFP) and carcinoembryonic
antigen (CEA)
 An ideal tumor marker has the following characteristics:
 It must be produced by the tumor or as a result of the tumor and must be
secreted into some biological fluid that can be analyzed easily and
inexpensively for levels.
 Its circulating half-life must be long enough to permit its concentration to
rise with increasing tumor load.
 It must increase to clinically significant levels (above background control
levels) while the disease is still treatable and with few false negatives
(sufficient sensitivity).
 The antigen must be absent from or at background levels in all
individuals without the malignant disease in question to minimize false-
positive test results (sufficient specificity).
 can provide important adjunct information to patient histories
and physical exams
 tests include stool occult blood and colonoscopy for
colorectal carcinoma, Papanicolaou smear for cervical
cancer, self-exams for breast and testicular cancer, x-ray
mammography for breast cancer, and digital rectal exam for
prostate cancer
 three types of laboratory methods for cancer screening and
diagnosis are gross and microscopic morphology of tumors,
detection of antigen/protein tumor markers, and DNA/RNA
molecular diagnostics
 the choice of method often depends on convenience, cost,
sensitivity, and specificity
 Some of the molecular diagnostic techniques that have
become increasingly routine include the following:
1. Cytogenetic studies:
 Many cancers are associated with particular karyotypes. However,
as more precise knowledge of the exact gene defects present in
various cancers is gained, testing for the aberrant genes is
becoming more prevalent.
2. Nucleic acid amplification techniques:
 Polymerase chain reaction (PCR) and its variants increase
the inherent level of DNA or RNA, allowing the detection of
small populations of cancer cells (including circulating cells in
metastasis) and the detection of mutations, deletions, and
gene rearrangements/translocations
3. Fluorescent in situ hybridization (FISH)
 Nucleic acid probes capable of binding to sequences of
interest are tagged with fluorophors and applied to cells.
Cells containing the sequence of interest can be visualized
with fluorescent microscopes. Similar techniques using
nonfluorescent labels such as enzymes and silver stains are
also becoming available.
 Proteomics
 new field that employs mass spectrometry (MS) to identify and quantify
an array of proteins simultaneously present in a sample. This has given
birth to a new field called oncopeptidomics (defined as application of
peptidomics technologies to the field of oncology)
 Protein profiling in cancer patients will aid in the discovery of new tumor
markers or patterns of protein expression that are consistent with cancer.
 Oncopeptidomics may allow more subtle increases of tumor markers to
have diagnostic significance, since multiple markers can be measured
and the overall pattern assessed, but this is currently only at the research
stage
 final aspect of tumor immunology
1. Passive immunotherapy-involves transfer of antibody,
cytokines, or cells to patients who may not be able to mount
an immune response.
-many barriers because of possible recipient rejection of foreign cells,
graft-versus host disease (GVHD), and the fragility of live cells.
2. Active immunotherapy- patients are treated in a manner that
stimulates them to mount immune responses to their
tumors.
Ex. Adjuvants such as BCG