Neoplasia and tumor immunology

Question 1

What are the three steps in multi-stage carcinogenesis?

Answer 1

1. initiation: cells are genetically altered, but remain dependent on normal metabolic pathways
2. promotion: clonal expansion of genetically
3. progression: genetic and phenotypic changes required for malignancy

Question 2

How does inflammation lead to carcinogenesis?

Answer 2

Inflammation causes the generation of promutagenic reactive oxygen species. This alters the regulation of parenchymal cells

Question 3

What are the four phenotypic hallmarks of cancer?

Answer 3

1. Deregulation of cellular energetics
2. Genomic instability
3. Avoidance of immune destruction
4. Tumor - promoting inflammation

Question 4

What is the evidence that the immune system is important for preventing tumors?

Answer 4

1. Risk of cancer increases in immunosuppressed patients
2. HIV pts develop kaposi’s sarcoma/hodgkin’s lymphoma
3. Cancer is more prevalent in the elderly, when immune system is not as strong

Question 5

What are inflammatory diseases in carcinogenesis?

Answer 5

1. ulcerative colitis
2. Hep B and C
3. Chronic pancreatitis
4. H pylori

Question 6

What is immunoediting?

Answer 6

Modification of self characteristics to avoid detection by immune system. Through this process, cancer cells can progress from elimination to equilibration to escape.

Question 7

How do immune cells recognize cancer?

Answer 7

1. Tumor cells with loss of MHC I are recognized by NK cells and killed
2. T cells can recognize tumor specific antigen cells
3. B cells crete tumor-specific antibodies

Question 8

What tumor antigens can the immune system recognize?

Answer 8

1. Viruses that cause cancer
2. Fetal antigens expressed by cancer cells
3. Immune system can detect mutations expressed by cancer cells
4. Viral, fetal, or mutated antigens
5. Normal antigens expressed by tumor cells (ex: vitilligo)

Question 9

How do cancer cells evade the immune system?

Answer 9

1. Antigen loss (loss of MHC)
2. Induction of T reg cells to release IL-10 and TGF-beta
3. Myeloid derived suppressor cells
4. Release of tumor suppressors

Question 10

Describe the relationship between HCV and hepatocellular carcinoma

Answer 10

1. May generate reactive oxygen-species
2. Increase cell division

OR

Proteins from viral genome interact with and inactivate tumor suppressor gene products

Question 11

List the immune cells that can recognize cancer cells and describe the mechanism of tumor recognition used by each one

Answer 11

T cells activated by APC, which will undergo clonal expansion of cells with the right TCR

B cells produce anti-cancer antibodies

NK cells recognize loss of MHC I on cells and provides cell-mediated toxicity. Will also recognize and kill antibody-bound tumor cells

Question 12

What is the tumor microenvironment?

Answer 12

Normal host cells co-opted to follow tumor’s needs creating an abnormal microenvironment in the body

Question 13

How do tumor cells protect themselves?

Answer 13

Through immune evasion and immune suppression