Transcript C22 Cancer and the Immune System

C22 Cancer and the Immune System
• Cell births ~ cell deaths; production of new
cells is regulated
• Cells that do not respond to normal growth
controls can expand clonally -> form a
tumor (neoplasm)
– Benign tumors
– Malignant tumors (cancer)  metastasis
» 1° tumor  2° tumor
Tumor growth and metastasis
Classification of cancers
-according to embryonic origin
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>80% carcinoma
9% leukemia
1% sarcoma
tissue cells become transformed by
chemicals, radiation, and viruses – are
“immortal”
-involves initiation through somatic mutation and
promotion through loss of cellular controls
Oncogenes and cancer induction
• Oncogene=cancer inducing gene found in animal
cells and viruses
– Derived from cellular genes (proto-oncogenes)
involved with growth-controlling proteins
– Usually a mutation in proto-oncogene causes a rise in
expression of the proteins
• Function to regulate cell growth (proliferation) or
inhibition of cell proliferation or programmed cell
death
– Effects to genes produce uncontrolled proliferation or
blocks to cell inhibition (tumor-suppressor/antioncogenes) or suppress apoptosis
Conversion of proto-oncogenes to oncogenes
Model of sequential genetic alterations in
colon cancer – a multi-step process
the morphologic stages correspond to genetic changes to 3 tumor
suppressor genes and 1 cell proliferation gene
Tumors of the Immune system
• Lymphoma = solid tumors in lymph nodes/bone marrow/
thymus (Hodgkins or Non-Hodgkins)
• Leukemia = single cell increase; in either lymphoid/myeloid
– Acute vs chronic; acute in young, chronic in old/mature
– Good prognosis with both! Permanent remission often achieved
– ALL/AML or CLL/CML
Tumor Antigens
• Ag’s found on tumor cells
– May result from altered cell proteins or embryonic
proteins activated in adult cells or normal proteins
expressed at greater levels
– Can be presented on MHC I  induce T cell
activity
• Two types of tumor antigens identified:
– Tumor-specific transplantation ag’s (TSTA’s)
– Tumor-associated transplantation ag’s (TATA’s)
Mechanisms which generate
TSTA’s and TATA’s
Tumor Specific Antigens
• Identified through induction exp’ts using
chemical or physical or viral means
– Many are surface, many are cytosolic proteins
• Virally induced ag’s are similar for the same
virus
– EBV infected cells express a nuclear protein
– HPV cells express E6/E7 proteins (>80% of cervical cancers)
Potential of virally-induced tumor antigens seen
in animal models….next slide
Experimental induction of immunity vs. tumor cells
induced by polyoma virus (PV)