Pod Cancer

Front 1

What are the main features of cancer?

Back 1

Uncontrolled growth (contact inhibition is lost, apoptosis doesn't happen)

Front 2

Name and explain 3 molecular mechanisms leading to cancer.

Back 2

Point mutations: DNA Pol III makes an error in one AA (may be caused by smoking and/or irradiation)

Chromosomal translocations: segment of a gene is swapped to another (Burkitt's lymphoma)

Chromosomal deletion: deletion of genes for pro-apoptotic p53 will lead to this (dx using FISH)

Front 3

Explain the process leading to malignant transformation.

Back 3

Usually several single point mutations with either loss of suppressor genes or activation of anti-apoptotic genes is needed to produce cancer

Front 4

Describe 3 environmental agents causing cancer.

Back 4

Chemicals and radiation (e.g. cigarette smoke)

Infections
HPV -- blocks genes involved in induction of apoptosis
HepB -- chronic inflammation (angiogenesis develops to maintain flow of lymphocytes but also brings oxygen and nutrients to a tumor)

Front 5

Describe the events in chronic inflammation leading to cancer.

Back 5

See increased cell proliferation, evasion from apoptosis, and angiogenesis.

Angiogenesis maintains demand for lymphocytes and nourishes a tumor too by bringing in oxygen and nutrients.

Front 6

What is the role of cell communication in induction of cancer?

Back 6

Tumor cell - host stromal cell communication, epigenic alterations, and upregulation of inflammatory mediators leads to malignancy

Front 7

What are 5 inflammatory cytokines and chemokines involved in induction of cancer?

Back 7

Overproduction of IL-1 and IL-17

Chemokines promote tumor cell proliferation

NO promotes tumor growth and stimulates cell proliferation

TNF may play a role in skin and adrenal gland carcinomas

IL-6 is assoc with colon cancer, melanomas, plasmacytomas

Front 8

What are the advantages of cancer growing in a sterile environment?

Back 8

No danger signals are produced so the innate immune system is not activated

Front 9

How does a growing cancer avoid the innate immune system?

Back 9

Secretes anti-inflammatory cytokines (TGFbeta or MIF) to inhibit innate immune response

MIC usually displayed on surface of cells is a red flag for NK cells - cancer cells can secrete this so soluble MIC distracts NK cells

Front 10

How do we know the adaptive immune system fights cancer?

Back 10

Tumors can "transplant" cancer

Tumors can be irradiated and act as a vaccine (CD8 T cells main ones involved in protection once exposed to killed tumor)

Front 11

What adaptive immune system cells are most important in fighting cancer?

Back 11

CD8 T cells (incubated with IL-2 to make LAK cells that kill cancer cells)

Front 12

What are some tumor-associated antigens in humans?

Back 12

Those expressed in the embryo, in privileged sites, those not in contact with the blood, or those found in very low levels in nl cells but high levels in cancer cells (non-self antigens presented by MHC-I so T cells that can fight them are not negatively selected for)

Front 13

What mechanisms are involved in the activation and suppression of tumor growth?

Back 13

Tumor growth is activated if balance between DC cytokines (mature DCs release inflammatory cytokines like IL-12, TNF, IFNgamma and immature DCs secrete anti-inflammatory cytokines like IL-6) and tumor cytokines leans toward anti-inflammatory molecules and CD4 TH2 and Treg cells are activated.

Tumor growth is suppressed if balance between DC cytokines and tumor cytokines leans toward inflammatory molecules and TH1 CD8 T cells are activated.

TUMOR GROWTH-->immature DCs, IL-6,10,4,13, TGFbeta, CD4 TH2 cells and Treg cells

TUMOR SUPPRESSION -->mature DCs, TNF, IL-12,2, IFNgamma, HSP, MCP-1, CD8 TH1 T cells

Front 14

How is allogeneic and autologous cell transplantation done?

Back 14

Allogeneic - cells of pt are replaced by stem cells form a donor; involves chemotherapy and irradiation, HLA-matched bone marrow cells put in

Autologous - obtain stem cells from patient (assuming they are not so far progressed that they still have viable ones), mobilize bone marrow cells with GM-CSF and G-CSF and positively select stem cells with anti-CD34 antibodies; after this, treat with chemo and radiation and inject the CD34+ cells back into the patient to reconstitute their immune system

Front 15

What are 3 strategies for adoptive transfer of CD8 T cells?

Back 15

Use LAK cells (pts own CD8 cells activated in vitro with IL-2) -- must get into the tumor though which can be hard

Use TILs (tumor-infiltrating lymphocytes) -- these are obtained from a biopsy of the tumor, activated with IL-2, and reinjected

Lympho-depletion of tumors -- when inject TILs, there are often some types of immune cells there which may be secreting anti-inflammatory cytokines and inadvertently helping the tumor so want to get rid of those so TILs can get in there and do their job

Front 16

Why is lympho-depletion done before CD8 transplantation in solid tumors?

Back 16

There are lymphocytes in the tumor that are allowed to stay bc they are secreting anti-inflammatory cytokines and so they downregulate TILs and must be killed if CD8 transplantation will work.

Presence of mast cells in a tumor indicates a poor prognosis.

Front 17

How are therapeutic vaccines based on dendritic cells used?

Back 17

DCs can be injected with exogenous antigen and present it to CD4 and CD8 T cells on their MHC-I

Could use HSPs as adjuvants

Front 18

Explain the concept of the magic bullet.

Back 18

Antibodies can be conjugated to a toxin or radionucleotide and injected into a patient and it will find the target it is specific for and kill it because of the toxin/radionucleotide

Front 19

Describe 3 types of monoclonal antibodies.

Back 19

Chimeric - 25% mouse, 75% human (immune system may react against mouse parts), easiest to make
--Rituximab

Humanized - 5% mouse, 95% human, less chance of reaction, harder to make
--Trastuzumab

Fully human - hardest to get, least chance of reaction

Front 20

How is rituximab used? How does it work?

Back 20

Chimeric monoclonal antibody that is used against cancer.

It attacks B cells by binding to CD20 and thus inducing apoptosis. Complement is also activated by this as well as ADDC (involves NK cells)

Front 21

What is trastuzumab used for and how?

Back 21

Trastuzumab is used against cancer and is a monoclonal humanized antibody. It is only useful in people who have breast cancer with over-expressed Her2/neu because it binds that receptor for human epidermal growth factor. This arrests the cell in G1 (cytostatic) and can also causes ADDC (cytotoxic)

Front 22

What are two vaccines against oncogenic viruses?

Back 22

Hep B
HPV

Front 23

What are virus-like particles (VLPs)?

Back 23

Structures used in vaccines that look like viruses but contain no genetic material (gene for protein of virus is put onto plasmid then into a yeast where it is induced to be translated, then proteins are assembled into a virion)

Front 24

How were the HPV and Hep B vaccines developed?

Back 24

Genes for proteins unique to virus were identified, put onto plasmid, placed in yeast, translated there, and then assembled into a VLP.

Front 25

Why don't the HPV and Hep B vaccines eliminate an already-existing infection?

Back 25

Makes neutralizing antibodies that can eliminate early infection but not an established one.