LEC 11

Question 1

What is cancer?

Answer 1

Refers to diseases caused by malignant tumors

Question 2

What do you call cancer of epithelial origin?

Answer 2

carcinoma

Question 3

What to you call cancer of hematopoietic origin?

Answer 3

circulating cells = leukemia

solid lymphoid tumors = lymphomas

bone marrow = myeloma

Question 4

What to you call cancer of mesodermal connective tissue?

Answer 4

sarcomas

i.e. bone, fat, cartilage

Question 5

Where does cancer commonly arise from?

Answer 5

tissues that are actively undergoing cell division

Question 6

What can induce malignant transformation?

Answer 6

accumulated DNA mutations

• chemical substances
• physical agents
• ionizing radiation
• viruses

mutagens = carcinogens

Question 7

What is a malignant transformation?

Answer 7

changes that occur in a cell to make it cancerous

Question 8

What are genes concerned with cell multiplication and survival?

Answer 8

Proto-oncogenes - genes that normally contribute positively to initiation and execution of cell division

Tumor suppressor genes - encode proteins that prevent unwanted proliferation of mutant cells (p53)

Question 9

What are the mutant forms of proto-oncogenes called?

Answer 9

(cellular) oncogenes

Question 10

Sequential genetic alteration leading to metastatic cancer

Answer 10

Normal epithelium

Hyper-proliferative epithelium

Early adenoma

Intermediate adenoma

Late adenoma

Carcinoma

Metastasis

Question 11

What are some hallmarks of cancer?

Answer 11

Sustaining proliferative signaling

Evading growth suppressors

Activating invasion and metastasis

Enabling replicative immortality

Inducing angiogenesis

Resisting cell death

Question 12

What are some emerging hallmarks and enabling characteristics of cancer?

Answer 12

EMERGING HALLMARKS

Avoiding immune destruction

Tumor-promoting inflammation

ENABLING CHARACTERISTICS
Genome instability and mutation

Deregulating cellular energetics

Question 13

Some proposed mechanisms for immune system control of cancer

Answer 13

Destruction of viruses that are known to transform cells

Elimination of pathogens and reduction of pro-tumor inflammation

Active identification and elimination of cancerous cells (immunosurveillance)

Question 14

What is immunosurveillance?

Answer 14

Active identification and elimination of cancerous cells

Question 15

Immune mechanisms of cancer eradication

Answer 15

1. Natural Killer Cells detect tumor cells via: i. loss of MHC class I = missing self
   ii. upregulation of NKG2D ligands (altered self) on tumor cells due to cellular stress → directly kill and release IFNγ
2. Macrophages observed to cluster around tumors and may mediate ADCC, also secrete TNFα
3. Cytokines: IFNγ induces upregulation of MHC class I = better CD8 T cell detection IL-12 – perhaps through DCs to activate strong TH1 and CD8 responses TNFα can induce hemorrhage and necrosis of tumors
4. Humoral and cell-mediated adaptive immune responses via recognition of tumor antigens

Question 16

Tumor antigens are unique or inappropriately expressed self-antigens

Answer 16

Tumor-specific antigens (TSA): antigens present on tumor cells but not on normal cells

Tumor-associated antigens (TAA): antigens present on tumor cells as well as normal cells (but smaller amounts or developmentally expressed)

Question 17

What are TAAs?

Answer 17

Tumor-associated antigens (TAA)

antigens present on tumor cells as well as normal cells (but smaller amounts or developmentally expressed)

Question 18

What are TSAs?

Answer 18

Tumor-specific antigens (TSA): antigens present on tumor cells but not on normal cells

Question 19

The immune system plays an important role in protecting against cancer BUT

Answer 19

BUT, chronic inflammation and immune-mediated selection for malignant cells may CONTRIBUTE to cancer cell spread and survival

Question 20

________ can promote tumor growth

Answer 20

Immunoediting can promote tumor growth

Phase 1: Elimination

Phase 2: Equilibrium

Phase 3: Escape

Question 21

Down-regulation of _______ may allow tumor escape mutants

Answer 21

MHC class I

Question 22

Cancer Immunotherapy

Answer 22

1. Monoclonal Antibodies targeted to tumor cells
   → used unmodified or conjugated with agents that increase efficacy (e.g. toxins, chemical agents, radioactive particles)
   = immunotoxins
2. Adoptive T Cell Therapy
   → isolate tumor-specific T cells from patient, expand and activate them ex-vivo, and then re-infuse into patient
3. Therapeutic Vaccines
4. Manipulate co-stimulatory signals