2Th 11:00Am - L22: Tumor Immunology

Front 1

If a mouse's sarcoma is resected and transplanted into a normal mouse of the same strain (ie: it has the same MHC), what will happen to the recipient mouse?

Back 1

It will grow a tumor

Front 2

If a mouse's sarcoma is resected and transplanted back onto the same original mouse (which had been cured by the surgical removal of the tumor), what will happen in this mouse?

Back 2

It will reject the subsequent transplant of the same tumor

Front 3

If killed cells from a mouse's sarcoma are injected into the mouse, what happens in that mouse?

Back 3

Protective immunity is induced to that tumor

Front 4

If killed cells from an unrelated tumor is injected into a mouse, what happens to that mouse?

Back 4

Protective immunity to the tumor is not induced.

Front 5

If CD8+ cytotoxic T lymphocytes are adoptively transferred from an mouse immune to a tumor, what will happen in the recipient mouse?

Back 5

Immunity to the transplanted tumor will be achieved.

Front 6

What are 4 types of tumor antigens?

Back 6

(1) Mutated cellular proteins unrelated to the malignant phenotype
(2) Mutated cellular proteins related to the malignant phenotype (oncogenes or tumor suppressor genes)
(3) Overexpressed or aberrantly expressed cellular proteins
(4) Proteins encoded by oncogenic viruses

Front 7

What is the mechanism by which cytotoxic T lymphocytes (CTL) contribute to tumor rejection?

Back 7

They are directed against MHC I-bound antigens expressed by the tumors.

Front 8

What is the mechanism by which natural killer (NK) cells contribute to tumor rejection?

Back 8

NK cells often kill tumor cells indiscriminately with respect to their origin. They are most efficient at killing tumor cells that express low levels of MHC I molecules, and can kill cells that are coated with IgG antibodies, via antibody-dependent cellular cytotoxicity (ADCC)

Front 9

What is the mechanism by which antibodies contribute to tumor rejection?

Back 9

They are directed against tumor antigens, but are less important than CTL and NK cell responses

Front 10

What is the mechanism by which macrophages contribute to tumor rejection?

Back 10

They phagocytose opsonized tumor cells, and can kill tumor cells by production of TNF. Cytokines produced by TH1 cells may recruit macrophages to the tumor.

Front 11

What are 3 ways that tumors escape recognition by the immune system?

Back 11

(1) low immunogenicity
(2) antigenic modulation
(3) immunosuppression

Front 12

Explain how tumors escape recognition by the immune system by low immunogenicity

Back 12

Tumor cells often do not express adhesion molecules, MHC I or II molecules, tumor-specific antigens, or co-stimulatory molecules (ie. B7).

Front 13

Explain how tumors escape recognition by the immune system by antigenic modulation

Back 13

Tumor cells may lose antigens that the immune system can recognize due to mutations. Antigen-loss variants may not be recognized by the immune system.

Front 14

Immunosuppession

Back 14

Tumors often secrete factors, such as transforming growth factor β (TGF-β), which suppress immune responses

Front 15

What are 4 categories of immunotherapies for cancer?

Back 15

(1) Non-specific immune activators
(2) Antibodies
(3) Cellular approaches
(4) Therapeutic vaccines

Front 16

What are 3 non-specific immune activators in cancer immunotherapy?

Back 16

(1) pro-inflammatory stimuli
Eg: BCG to treat bladder cancer; imiquimod to treat skin cancers
(2) recombinant cytokines
Eg: IL-2 to treat advanced melanoma and renal cell carcinoma; IFN-α with chemotherapy to treat melanoma
(3) blockade of inhibitory pathways
Eg: Antibodies against inhibitory molecules such as CTLA-4 (cytotoxic T lymphocyte antigen-4) or PD-1 (programmed death-1)

Front 17

What are 3 antibody-based approaches in cancer immunotherapy?

Back 17

(1) Get tumor-specific antibodies to bind to tumor cells -> NK cells with Fc receptors (CD16) are activated to kill the tumor cells
(2) Get toxin-conjugated antibodies to bind to tumor cells -> Conjugates are internalized, killing the cell
(3) Get radionuclide-conjugated antibodies to bind to tumor cells -> Radiation kills the tumor cell and neighboring cells

Front 18

What are 2 cellular approaches in cancer immunotherapy?

Back 18

(1) Adoptive transfer of lymphokine activated killer (LAK) cells:
Isolate pt's lymphocytes -> culture in vitro with IL-2, activating and proliferating NK cells in the culture -> reintroduce LAK cells into pt, with IL-2
(2) Adoptive transfer of tumor infiltrating lymphocytes (TIL):
Isolate lymphocytes (mainly cytotoxic T cells) from tumor tissue -> culture in vitro with tumor cells (needed to present antigen to the T cells) and IL-2 -> re=-introduce TIL in pt, with IL-2

Front 19

Apart from vaccinating cancer patients with tumor antigens specific to a tumor (feasible only for tumors expressing common antigens), what are 2 therapeutic vaccine approaches in cancer immunotherapy?

Back 19

(1) Transfection of tumor cells with genes encoding cytokines or co-stimulatory molecules such as B7. B-7 expressing tumor cells stimulate naive T cells and elicit CTL responses. Local production of cytokines augment specific T cell responses against tumor antigens.
(2) Vaccine against prostate cancer, "Provenge", pulses dendritic cells with prostate-derived antigens