Tumor Immunology Prt 2 Flashcards

1
Q

SERUM TUMOR MARKERS

Limitations
- Can be elevated in benign conditions
(endometriosis) and other malignancies
• Increase during pregnancy and menstruation

A

CANCER ANTIGEN 125 (CA 125)

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2
Q

Clinical Applications
• Screening, diagnosis, prognosis, and monitoring response to therapy in ovarian cancer

A

CANCER ANTIGEN 125 (CA 125)

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3
Q

Structure
• Large, heavily glycosylated, mucinlike protein
• Lacks sensitivity and specificity

A

CANCER ANTIGEN 125 (CA 125)

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4
Q

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

A

CARCINOEMBRYONIC ANTIGEN (CEA)

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5
Q

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

A

CARCINOEMBRYONIC ANTIGEN (CEA)

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6
Q
  • First oncofetal antigen discovered in 1965 by Gold and Freedman

• Glycoprotein with molecular weight of 180,000 to 200,000

A

CARCINOEMBRYONIC ANTIGEN (CEA)

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7
Q

• Limitations
• Elevated in gonadal suppression caused by chemotherapy and do not necessarily indicate tumor recurrence

A

HUMAN CHORIONIC GONADOTROPIN (hCG)

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8
Q
  • “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
A

HUMAN CHORIONIC GONADOTROPIN (hCG)

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9
Q

• Limitations
• Elevated in benign prostatic hyperplasia (BPH) and prostatitis

A

PROSTATE-SPECIFIC ANTIGEN (PSA)

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10
Q

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

A

PROSTATE-SPECIFIC ANTIGEN (PSA)

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11
Q
  • 28,000 MW glycoprotein produced by prostate epithelial
    • First discovered in semen
A

PROSTATE-SPECIFIC ANTIGEN (PSA)

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12
Q

LABORATORY DETECTION OF TUMORS

LABORATORY METHODS

A

Tumor Morphology (Gross and microscopic)
Tumor Marker Detection (Immunohistochemistry or Automated
Immunoassays)
Molecular Diagnostics (Genetic mutations)

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13
Q

• Main use: cancer screening and diagnosis

A

Laboratory methods

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14
Q

LABORATORY METHODS

  1. Tissue Processing
    - Pathologists and histology labs process suspected tumor tissue through gross dissection and slide preparation.
  2. Microscopic Analysis
    - Slides are examined microscopically, often enhanced with tumor marker antibodies, special stains, and nucleic acid probes.
  3. Diagnosis
    • Final diagnosis requires considerable skill and is supplemented with clinical information and additional testing.
A

TUMOR MORPHOLOGY

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15
Q

LABORATORY METHODS

  1. Technique
    - Uses labeled antibodies to detect tumor antigens in formalin-fixed or frozen tissue sections.
  2. Process
    • Involves applying primary and secondary antibodies, with visualization through light or fluorescent microscopy.
  3. Application
    - Effective for classifying tumors of uncertain origin and identifying specific markers for precise tumor classification.
A

IMMUNOHISTOCHEMISTRY

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16
Q
  1. Advantages
    • Highly sensitive, automated, and relatively easy to use for measuring serum tumor markers.
  2. Challenges
    • Variability in antibody reagents, cross-reactivity issues, and potential for antigen excess leading to the high-dose hook effect.
  3. Considerations
    - Importance of consistent methods for patient monitoring and awareness of potential interferences from endogenous antibodies.
A

IMMUNOASSAYS FOR CIRCULATING TUMOR MARKERS

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17
Q

• 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.

A

MOLECULAR TECHNIQUES IN CANCER DIAGNOSIS

18
Q

• 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.

A

PROTEONOMICS IN CANCER RESEARCH

19
Q
  • immune system continually patrols the body for the presence of cancerous or precancerous cells and eliminates them before they become clinically evident
A

THEORY OF IMMUNOSURVEILLANCE

20
Q
  • 1950s F. Mactarlane Burnet and Lewis Thomas
A

THEORY OF IMMUNOSURVEILLANCE

21
Q

High Cases of Cancer
transplant patients who received…

patients with ____diseases

after the age of___

A

immunosuppressive therapy

immunodeficiency

60

22
Q

IMMUNE DEFENSES AGAINST TUMOR CELLS

INNATE IMMUNE RESPONSE

A

NK cells

Macrophages

Lymphokine-Activated Killer (LAK) Cells

23
Q

• 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

A

NK Cells

24
Q

• when activated by IFNy, they can kill tumor cells using mechanisms similar to those used against infectious organisms.
• produce TNF-a

A

Macrophages

25
Q

IMMUNE DEFENSES AGAINST TUMOR CELLS

ADAPTIVE IMMUNE RESPONSE

A

Cytotoxic T Lymphocytes (CTLS)

T Helper Cells

Antibodies

26
Q

• kill tumor cells through complement-mediated lysis or antibody-dependent
cellular cytotoxicity (ADCC), though their in vivo relevance is unclear.

A

Cytotoxic T Lymphocytes (CTLS)

27
Q

ADAPTIVE IMMUNE RESPONSE

• secrete cytokines like IL-2 and IFNy, which enhance CTL development and NK
cell activity, and activate macrophages.

A

• T Helper Cells

28
Q

• primary mediators of adaptive immunity against tumors
• activated by dendritic cells presenting tumor antigens
• use perforin and granzymes to induce apoptosis in tumor cells.

A

Cytotoxic T Lymphocytes (CTLS)

29
Q

• secrete cytokines like IL-2 and IFNy, which enhance CTL development and NK
cell activity, and activate macrophages.

A

• T Helper Cells

30
Q

• kill tumor cells through complement-mediated lysis or antibody-dependent
cellular cytotoxicity (ADCC), though their in vivo relevance is unclear.

A

Antibodies

31
Q

IMMUNOEDITING AND TUMOR ESCAPE

Robust innate and adaptive immune responses kill most tumor cells

Tumor cells identified by antigen and MHC 1; induced to apoptosis by FAS ligand

A

Elimination phase

32
Q

IMMUNOEDITING AND TUMOR ESCAPE

Immune system controls limited number of altered cells

Tumor cells dormant; begin to lose or mask identifying features

A

Equilibrium

33
Q

IMMUNOEDITING AND TUMOR ESCAPE

Immune system suppressed; chronic inflammation promotes tumor growth

Tumor cells highly altered and more resistant to immune responses; apoptosis impaired

A

Escape

34
Q

___________
To identify cancer in asymptomatic individuals in a population.

_________
To identify cancer in a particular patient.
Presence of the marker or an elevation of the marker above normal levels suggests the presence of the cancer.
_________
To predict the clinical outcome of a cancer patient and aid in therapeutic decision making.
An initial high concentration or an increasing level of the tumor marker over time indicates a worse prognosis.
________
To observe the response of a cancer patient to treatment.
Effective treatment is indicated by decreasing levels of the marker over time.

A

Screening

Diagnosis

Prognosis

Monitoring

35
Q

___________
Antigens that are unique to a tumor or shared by tumors of the same type

___________
Antigens that are expressed in normal cells as well as tumor cells

___________
Expressed in many tumors but not in most normal tissues

____________
Expressed on immature cells of a particular lineage

__________
Found in higher levels on malignant cells than on normal cells

A

Tumor-specific antigens (TSAs)

Tumor-associated antigens (TAAs)

Shared TSAs (cancer/testis antigens)

Differentiation antigens

Overexpressed antigens

36
Q

Burkitt lymphoma
Hodgkin lymphoma
Leiomyosarcomas
Post-transplant lymphoprolif-erative disease
Nasopharyngeal carcinoma

A

Epstein-Barr virus (EBV)

37
Q

Hepatocellular carcinoma

A

Hepatitis B virus (HBV)
Hepatitis C virus (HCV)

38
Q

Kaposi sarcoma

A

Human herpes virus 8
(HHV-8)

39
Q

Cervical cancer
Other genital and anal cancers
Head and neck cancer

A

Human papilloma virus (HPV)

40
Q

Adult T-cell leukemia or lymphoma

A

Human T-lymphotropic virus I (HTLV-1)

41
Q

Merkel cell carcinoma (a type of skin cancer)

A

Merkel cell polyomavirus