TUMOR IMMUNOLOGY Flashcards
•the enlargement of cell volume or tissue without increase in cell number
•Hypertrophy
Enlargement of tissue or organ by increased numbers of cells without change in volume of the cells
•Hyperplasia
• replacement of a given differentiated tissue, with another differentiated tissue having the same embryonic origin.
Metaplasia
• Pathological process characterized by an
overgrowth of tissue consisting of atypical cells,
characterized by a self-growing, progressive,
irreversible and non-finalistic behavior.
Neoplasia
• An abnormal mass of tissue that results from the
uncontrolled growth of normal cells even after the
growth stimulus is removed
Neoplasia
• Typically, a mild and non-progressive tumor
that pushes aside normal tissue but does not
invade it as the tumor expands
•Benign Tumor
• Generally consisting of poorly
differentiated cells that grow rapidly
and invade surrounding tissue, robbing
the normal tissue of nutrients
•Malignant Tumor
• Secondary tumor derived from a
malignant primary tumor
•Metastatic tumor
CLASSIFICATION OF TUMORS
•Benign Tumor
•Malignant Tumor
•Metastatic tumor
CLASSIFICATION OF MALIGNANT TUMORS
•According to tissue of origin
- Carcinomas
- Leukemias or lymphomas
- Sarcomas
STAGING SYSTEMS
- Numbered staging system
- TNM system
CANCER STAGING: TNM SYSTEM
• T (Tumor)
• 0 to 4
• N (Nodes)
• 0 to 3
•M (Metastasis)
• 0 to 1
CARCINOGENESIS
•A multistep process involving a series of
genetic mutations that cause the
phenotype of a cell to be changed over
time
CARCINOGENESIS
•Transformation of a cell into a malignant
tumor
GENES INVOLVED IN MALIGNANT
TRANSFORMATION
- Proto-oncogenes
- Tumor suppressor genes
Normal genes that have a positive influence
on cell proliferation and development.
- Proto-oncogenes
Normally inhibits cell division
- Tumor suppressor genes
CHARACTERISTICS OF A
CANCEROUS CEL
- Sustained signaling of proliferation
- Resistance to cell death
- Ability to induce angiogenesis (development of
new blood vessels to provide oxygen and nutrients
to the tumor) - Immortality in terms of cell division
- Invasion and metastasis
- Ability to avoid suppressors of cell growth
FOUR ADDITIONAL CHARACTERISTICS
OF A CANCEROUS CELL
- Reprogramming of energy metabolism to support
malignant proliferation - Ability to evade destruction by the immune
system - Genomic instability and mutations
- Inflammatory responses that promote tumor
growth
TUMOR ANTIGENS: TWO GROUPS
- Tumor-specific antigens (TSA’s)
- Tumor-associated antigens (TAA’s)
•Unique to tumor cells
- Tumor-specific antigens (TSA’s)
•Also found on normal cells
- Tumor-associated antigens (TAA’s)
They are coded for by viral oncogenes or by
host proto-oncogenes or tumor suppressor
genes that have undergone genetic
mutations
TUMOR SPECIFIC ANTIGENS
Arise from: reciprocal translocation, point mutations
• C-ABL, p53
TUMOR SPECIFIC ANTIGENS
Can also be produced by mutations induced by
carcinogenic chemicals
TUMOR SPECIFIC ANTIGENS
Expressed in both normal cells as well
as in tumor cells
TUMOR-ASSOCIATED ANTIGENS
TUMOR-ASSOCIATED ANTIGENS
•Categories:
- Shared TSAs
- Differentiation antigens
- Overexpressed antigens
• Expressed in many tumors, but not in most
normal tissues
TUMOR-ASSOCIATED ANTIGENS:
SHARED TSAS
• The only normal cells in which they have been
detected are testicular germ cells (i.e.,
spermatogonia and spermatocytes) and, to a
lesser extent, placental trophoblasts and
ovaries.
TUMOR-ASSOCIATED ANTIGENS:
SHARED TSAS
• The only normal cells in which they have been
detected are testicular germ cells (i.e.,
spermatogonia and spermatocytes) and, to a
lesser extent, placental trophoblasts and
ovaries.
• Melanoma antigen gene (MAGE)
TUMOR-ASSOCIATED ANTIGENS:
DIFFERENTIATION ANTIGENS
• Expressed on immature cells of a particular
lineage BUT not on mature B cells
• E.g., CD10 antigen (CALLA)
• Also includes the oncofetal or embryonic
antigens that are normally expressed on
developing cells of the fetus but not on cells in
the adult
TUMOR-ASSOCIATED ANTIGENS:
DIFFERENTIATION ANTIGENS
Examples of oncofetal antigens:
• CEA
• AFP
• PSA
• Found in higher levels on malignant cells than
on normal cells
TUMOR-ASSOCIATED ANTIGENS:
OVEREXPRESSED ANTIGENS
As a result of genetic mutations and amplifications
TUMOR-ASSOCIATED ANTIGENS:
OVEREXPRESSED ANTIGENS
As a result of genetic mutations and amplifications
• HER2
• CA125
• CA 19-9
• Biological substances that are found in
increased amounts in the blood, body
fluids, or tissues of patients with a specific
type of cancer
TUMOR MARKERS
• Concentration in serum depends on:
degree of tumor proliferation, size of tumor
mass and the proteolytic activities of the
tumor/ release from dying tumor cells
TUMOR MARKERS
CHARACTERISTICS OF AN IDEAL TUMOR
MARKER
- Be produced by the tumor itself or by the patient’s body in
response to the tumor - Be secreted into a biological fluid, where it can be
inexpensively and easily quantified - Have a circulating half-life long enough to permit its
concentration to rise with increasing tumor load - Increase to clinically significant levels above the reference
level while the disease is still treatable - Have a high sensitivity
- Have a high specificity
CLINICAL USES OF TUMOR
MARKERS
- Screening
- Diagnosis
- Prognosis
- Monitoring
Epstein-Barr virus (EBV
Burkitt lymphoma
Hodgkin lymphoma
Leiomyosarcomas
Post-transplant lymphoproliferative disease
Nasopharyngeal carcinoma
Hepatitis B virus (HBV)
Hepatocellular carcinoma
Hepatitis C virus (HCV
Hepatocellular carcinoma
Human papilloma virus (HPV)
Cervical cancer, other genital and anal cancers,
Head and neck cancer
Human herpes virus 8 (HHV-8)
Kaposi sarcoma
Human T-lymphotropic virus I (HTLV-1)
Adult T-cell leukemia or lymphoma
Merkel cell polyomavirus
Merkel cell carcinoma
