Tumor Immunology Prt 2 Flashcards
(41 cards)
SERUM TUMOR MARKERS
Limitations
- Can be elevated in benign conditions
(endometriosis) and other malignancies
• Increase during pregnancy and menstruation
CANCER ANTIGEN 125 (CA 125)
Clinical Applications
• Screening, diagnosis, prognosis, and monitoring response to therapy in ovarian cancer
CANCER ANTIGEN 125 (CA 125)
Structure
• Large, heavily glycosylated, mucinlike protein
• Lacks sensitivity and specificity
CANCER ANTIGEN 125 (CA 125)
Limitations
• Elevated in colitis, diverticulitis, irritable bowel syndrome, and nonmalignant liver disease
• Cigarette smoking can cause an increase in CEA level to nearly twice that of nonsmokers
• Elevated in other cancers: breast, gastrointestinal tract, pancreas, and lung
CARCINOEMBRYONIC ANTIGEN (CEA)
Clinical Applications
• Mainly used for monitoring patients undergoing therapy for colorectal cancer
• Detected with an average of 5 months before clinical symptoms appear
• Sensitive indicator of liver metastasis
CARCINOEMBRYONIC ANTIGEN (CEA)
- First oncofetal antigen discovered in 1965 by Gold and Freedman
• Glycoprotein with molecular weight of 180,000 to 200,000
CARCINOEMBRYONIC ANTIGEN (CEA)
• Limitations
• Elevated in gonadal suppression caused by chemotherapy and do not necessarily indicate tumor recurrence
HUMAN CHORIONIC GONADOTROPIN (hCG)
- “pregnancy hormone”
• Synthesized by trophoblasts during pregnancy
• 45,000 MW glycoprotein with a (LH, FSH, TSH) and B subunits
• Associated with germ cell tumors (ovary and testes) and choriocarcinoma - Measures intact hCG or hCG B subunit
HUMAN CHORIONIC GONADOTROPIN (hCG)
• Limitations
• Elevated in benign prostatic hyperplasia (BPH) and prostatitis
PROSTATE-SPECIFIC ANTIGEN (PSA)
Clinical Application
- Widely used marker for prostate cancer screening and monitoring
• PSA values, in conjunction with histological observation of prostate biopsy tissue, can be used to predict the stage of prostate cancer
PROSTATE-SPECIFIC ANTIGEN (PSA)
- 28,000 MW glycoprotein produced by prostate epithelial
• First discovered in semen
PROSTATE-SPECIFIC ANTIGEN (PSA)
LABORATORY DETECTION OF TUMORS
LABORATORY METHODS
• Tumor Morphology (Gross and microscopic)
• Tumor Marker Detection (Immunohistochemistry or Automated
Immunoassays)
• Molecular Diagnostics (Genetic mutations)
• Main use: cancer screening and diagnosis
Laboratory methods
LABORATORY METHODS
- Tissue Processing
- Pathologists and histology labs process suspected tumor tissue through gross dissection and slide preparation. - Microscopic Analysis
- Slides are examined microscopically, often enhanced with tumor marker antibodies, special stains, and nucleic acid probes. - Diagnosis
• Final diagnosis requires considerable skill and is supplemented with clinical information and additional testing.
TUMOR MORPHOLOGY
LABORATORY METHODS
- Technique
- Uses labeled antibodies to detect tumor antigens in formalin-fixed or frozen tissue sections. - Process
• Involves applying primary and secondary antibodies, with visualization through light or fluorescent microscopy. - Application
- Effective for classifying tumors of uncertain origin and identifying specific markers for precise tumor classification.
IMMUNOHISTOCHEMISTRY
- Advantages
• Highly sensitive, automated, and relatively easy to use for measuring serum tumor markers. - Challenges
• Variability in antibody reagents, cross-reactivity issues, and potential for antigen excess leading to the high-dose hook effect. - Considerations
- Importance of consistent methods for patient monitoring and awareness of potential interferences from endogenous antibodies.
IMMUNOASSAYS FOR CIRCULATING TUMOR MARKERS
• Nucleic Acid Amplification Techniques (NAAT)
- Detect genetic mutations
• Fluorescent In-Situ Hybridization (FISH)
- for detecting chromosomal abnormalities and gene amplification.
• Microarrays
- Testing for panels of genetic markers and comparing gene expression levels.
• Next Generation Sequencing (NGS)
- comprehensive genetic analysis of tumors.
MOLECULAR TECHNIQUES IN CANCER DIAGNOSIS
• 2D Electrophoresis
- Separates proteins based on their isoelectric point and molecular weight, coupled with mass spectrometry for identification.
• Surface-Enhanced Laser Desorption/lonization Time-of-Flight (SELDI-TOF)
- mass spectrometry for protein analysis.
• Antibody Arrays
- Multiplex protein detection using antibody-coated beads and fluorescent labeling, analyzed by flow cytometry.
PROTEONOMICS IN CANCER RESEARCH
- immune system continually patrols the body for the presence of cancerous or precancerous cells and eliminates them before they become clinically evident
THEORY OF IMMUNOSURVEILLANCE
- 1950s F. Mactarlane Burnet and Lewis Thomas
THEORY OF IMMUNOSURVEILLANCE
High Cases of Cancer
transplant patients who received…
patients with ____diseases
after the age of___
immunosuppressive therapy
immunodeficiency
60
IMMUNE DEFENSES AGAINST TUMOR CELLS
INNATE IMMUNE RESPONSE
NK cells
Macrophages
Lymphokine-Activated Killer (LAK) Cells
• kill tumor cells without prior sensitization
• activated by cells lacking class I MHC molecules (a common trait in transformed cells)
• most effective against malignant cells in the bloodstream during the early stages of tumor development
NK Cells
• when activated by IFNy, they can kill tumor cells using mechanisms similar to those used against infectious organisms.
• produce TNF-a
Macrophages
