Lecture 22

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Questions and Answers

What are the antigens expressed on tumor cells that are normally present on the cells of origin called?

Differentiation antigens (correct)

Tumor-specific antigens

Immune surveillance antigens

Lineage-specific markers

What is the primary mechanism of anti-tumor activity in immune surveillance?

Cell-mediated mechanisms (correct)

Complement-mediated mechanisms

Humoral-mediated mechanisms

Inflammation-mediated mechanisms

What is the consequence of selective outgrowth of antigen-negative variants during tumor progression?

Tumor cell differentiation

Increased immune response

Elimination of tumor cells

Decreased immune response (correct)

What is the effect of tumor cells failing to express HLA class I?

Escaping attack by CTLs Signup and view all the answers

What is the role of natural killer cells in immune surveillance?

First line of defense against tumor cells Signup and view all the answers

What is a consequence of immunosuppression in tumor-bearing hosts?

Increased frequency of cancer Signup and view all the answers

What is the purpose of antibodies against differentiation antigens in tumor immunotherapy?

To target tumor cells Signup and view all the answers

What is an example of a differentiation antigen used in diagnosing and treating lymphoma?

CD20 Signup and view all the answers

What are the two main categories of tumor antigens?

TTA and TSA Signup and view all the answers

What are the products of mutated proto-oncogenes and tumor suppressor genes classified as?

Class I tumor antigens Signup and view all the answers

What is an example of an overexpressed normal cellular protein in tumor cells?

Tyrosinase in melanoma Signup and view all the answers

What is the term for antigens that are encoded by genes that are silent in all normal adult tissues except the testis?

Cancer-testis antigens Signup and view all the answers

What is the name of the antigen that is re-expressed in colon cancer?

Carcinoembryonic antigen (CEA) Signup and view all the answers

What is the function of altered cell surface glycoproteins in tumor cells?

They are used as diagnostic markers and for targeted therapy Signup and view all the answers

What is the term for antigens that are expressed during embryogenesis but not in normal adult tissues?

Oncofetal antigens Signup and view all the answers

What is the main problem with the classification of tumor antigens into TTA and TSA?

Many antigens thought to be tumor-specific are expressed by normal cells Signup and view all the answers

What is the result of cachexia on the body?

Loss of body fat and muscle mass Signup and view all the answers

What is the percentage of patients with malignant disease that experience paraneoplastic syndrome?

10-15% Signup and view all the answers

What is the basis for grading a cancer?

Microscopic features, including degree of differentiation and number of mitoses Signup and view all the answers

What is the term for symptom complexes that occur in patients with cancer and cannot be explained by local or distant spread of the tumor?

Paraneoplastic syndrome Signup and view all the answers

What is the term for methods to quantify the extent and spread of tumors?

Staging Signup and view all the answers

What is the term for the process by which tumor cells secrete cytokines that induce proteolysis?

Ubiquitin proteosome pathway Signup and view all the answers

What is the term for tumors that are undifferentiated and highly malignant?

Grade IV Signup and view all the answers

What is the basis for staging of cancer?

Size of the primary lesion, extent of spread to lymph nodes, and presence of metastases Signup and view all the answers

What is the primary purpose of tumor staging systems?

To classify tumors into different categories Signup and view all the answers

What does the 'T' in TNM staging system represent?

Tumor size Signup and view all the answers

What is the purpose of molecular diagnosis in cancer patients?

All of the above Signup and view all the answers

What is the significance of detecting specific gene mutations in cancer diagnosis?

It confirms the presence of cancer Signup and view all the answers

What is the purpose of tumor markers in cancer diagnosis?

To monitor the effectiveness of treatment Signup and view all the answers

What is the role of PCR in molecular diagnosis of cancer?

To detect specific gene mutations Signup and view all the answers

What is the significance of stage IV in cancer staging?

Tumor has metastasized extensively Signup and view all the answers

What is the purpose of cytological smears in lab diagnosis of tumors?

To diagnose cancer Signup and view all the answers

Study Notes

Tumor Antigens

Tumor antigens are classified into two types: Tumor-Associated Antigens (TAA) and Tumor-Specific Antigens (TSA)
However, this classification is imperfect, and many TSA turned out to be expressed by some normal cells as well

Classification of Tumor Antigens

Products of mutated proto-oncogenes and tumor suppressor genes
Overexpressed or aberrantly expressed cellular proteins
Tumor antigens produced by oncogenic viruses
Oncofetal antigens
Altered cell surface glycolipids and glycoproteins
Cell type-specific differentiation antigens

Tumor Immunity

Immune surveillance: tumor cells can be recognized by the immune system as non-self and destroyed
Anti-tumor activity is predominantly mediated by cell-mediated mechanisms
CTL (Cytotoxic T lymphocytes) are the major immune defense against tumors
Natural Killer cells and macrophages also play a role in immune surveillance

Failure of Immune Surveillance

Cancer cells can evade immune surveillance in immunocompetent hosts through various mechanisms
Selective outgrowth of antigen-negative variants
Loss or reduced expression of histocompatibility molecules
Immunosuppression by oncogenic agents or tumor products

Effects of Tumor on Host

Benign and malignant neoplasms can cause problems due to:
- Location and pressure effects on adjacent tissues
- Functional activity, hormone production
- Ulcerations with bleeding and secondary infection
- Acute symptoms due to rupture or infarction
- Cachexia
- Paraneoplastic syndrome

Cachexia

Wasting of the whole body due to loss of body fat and body mass
Generalized weakness, anemia, anorexia due to cytokines secreted by tumor cells and host
Caused by tumor necrosis factor (TNF) secreted by macrophages

Paraneoplastic Syndrome

Symptom complexes that occur in patients with cancer and cannot be readily explained by local or distant spread of the tumor
Occur in 10-15% of patients with malignant disease
Can be the first manifestation of an occult neoplasm
May be lethal
Common in lung, breast cancer, and hematologic malignancies

Grading and Staging of Tumors

Grading of a cancer is based on microscopic features
- Degree of differentiation of tumor cells
- Number of mitoses
Grading: I (low grade, well-differentiated), II (moderate), III (poorly differentiated), IV (high grade, undifferentiated/anaplastic)
Staging of cancer is based on:
- Size of the primary lesion (T)
- Extent of spread to lymph nodes (N)
- Presence of metastases (M)
Staging has more prognostic value than grading

Lab Diagnosis of Tumors

Morphological methods:
- Microscopic diagnosis of tumors received in the lab as excisional biopsy, fine needle aspiration biopsy, cytological smear, or fresh sample for frozen section diagnosis
Tumor markers:
- Biochemical assays of tumor-associated hormones and other tumor markers in blood or serum
Molecular diagnosis:
- By PCR, FISH, and molecular profiling of tumors (DNA-microarray analysis)

Applications of Molecular Analysis

Diagnosis of malignancy
Prognosis and behavior
Detection of minimal residual disease
Detection of hereditary predisposition to cancer

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Description

Learn about the different types of tumor antigens, including Tumor-Associated Antigens (TAA) and Tumor-Specific Antigens (TSA), and how they are classified.