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Flashcards in Tumor Immunity Deck (17):
1

Tumor Antigen Recognition

Cancer cells express MHC class I (usually) but lack co-stimulatory molecules so CD8 cells cannot directly be activated by tumor cells. They require an APC to become activated (cross-presentation). Once CD8 CTL are activated, they mediate effector functions and can directly see MHC I/peptide (tumor antigen) and no longer require the presence of co-stimulatory proteins.

2

What are the two pathways by which T cells recognize tumor cells as "foreign?"

Exogenous pathway &
Endogenous pathway

3

Recognizes Class II MHC; APCs capture tumor proteins (shed or from dying cells) from the microenvironment, process the proteins and present the peptide antigens

Exogenous pathway

4

Tumor cells themselves can process cytoplasmic proteins into peptides (antigens) that get presented by MHC class I.

Endogenous pathway

5

What are some barriers to cancer immunity?

Expansion and recruitment of regulatory cells
Secretion of immunosuppressive cytokines

6

How can clinical responses to cancer cells be increased?

Cancer immunotherapy -- learning how to turn off the suppressive components of the immune response that prevent immune cells from recognizing and killing cancer cells

7

What are the three approaches to cancer immunotherapy?

1. Monoclonal antibodies
2. Adoptive cellular immunotherapy
3. Vaccines

8

Potential targets for monoclonal antibody therapy.

1. tumor associated blood vessels
2. vascular growth factors or their receptors
3. diffuse malignant cells
4. tumor cells within a solid tumor
5. tumor associated stroma

9

Two approved MAb.

Her2/Neu for breast cancer
CD20 (B cell marker) for B cell lymphoma

10

MAb's used to interfere with immune checkpoints

Immune checkpoints are inhibitory pathways that maintain self tolerance and modulate the duration/magnitude of an immune response

Examples: CTLA4, PD-1, LAG-3

11

What are possible monoclonal antibody mechanisms of action?

1. Unconjugated: must rely on complement, ADCC, direct clearance by other Fc receptor-bearing cells, or the ability to block interactions between receptors and ligands involved in cancer progression
2. Antibody conjugates:
3. T cell binding epitopes

12

Potential limitation of monoclonal antibodies

Mutation or down-regulation of tumor antigens; derived from mice or rats so they induce potent rejection response in humans

13

What are tumor-infiltrating lymphocytes (TILs)?

Lymphocytes cultured from tumors removed by surgery then expanded in culture and given back to the patients to provide large numbers of highly activated T cells that recognize the cancer cells -- one way to bypass the tumor suppressive mechanisms

14

What has adoptive T cell immunotherapy been effective for?

Advanced metastatic melanoma

One side effect is autoimmunity -- non-life threatening vitiligo, uveitis

15

What are Chimeric antigen receptors (CARs)??

T cells are genetically engineer to express proteins (CARs) that allow them to recognize a specific protein (antigen) on tumor cells -- they're grown in laboratory and then implanted into the patient

16

What are some of the risks associated with CARs?

1. T cells are so strongly activated that they make large amounts of pro inflammatory cytokines that result in Toxic shock-like syndrome
2. If the tumor antigen is also expressed on normal tissues there could be autoimmune toxicity
3. Tumor antigen may be lost
4. Does not work well for treating solid tumors

17

Explain graft vs tumor effect.

Donor T cells transferred to the host become activated to host alloantigens -- idea is to titrate the effect so there is enough alloreactivity that GVH is manageable but still want that to tarot residual host cancer