Hudig: Tumor Immunology

Question 1

Are tumors considered self or non-self?

Answer 1

tumors are similar to self and have few antigens, so immune responses to tumors are limited

**don’t generate IL-1, TNFalpha, and signal 2

Question 2

Give 3 reasons why immune responses to tumors are “weak.”

Answer 2

1. tumor antigens are tolerated as self
2. persistent immune responses lead to T cell exhaustion
3. tumors create a suppressive environment

Question 3

Tumorgenesis induces T cell (blank) – lack of inflammation and signal 2

Answer 3

anergy

Question 4

What are the 3 E’s on tumor immunity?

Answer 4

elimination: immunosurveillance of highly antigenic neoplasms
equilibrium: tumor growth and immune killing both occur
escape: tumor loses antigens, secretes inhibitory factors, grows out of control, etc…

Question 5

What phase is this: when tumors arise in the tissue, a number of immune cells can recognize and eliminate them

Answer 5

elimination phase

Question 6

What phase is this: variant tumor cells arise that are more resistant to being killed; over time, a variety of different variants emerge

Answer 6

equilibrium phase

Question 7

What phase is this: eventually, one variant may escape the killing mechanism or recruit regulatory cells to protect it and spread unchallenged

Answer 7

escape phase

Question 8

Tumor immunity is usually (blank) for individual tumors

Answer 8

specific

Question 9

What is the difference between tumor specific antigens and tumor associated antigens?

Answer 9

tumor specific antigens are found on tumors but not on normal cells (ex: papiloma viral ag’s in MHCI)
tumor associated antigens are found on both tumor and normal cells (ex: MAGE in melanoma or HER2 on breast cancer cells0

Question 10

What are these: products of mutated oncogenes and tumor suppressor genes

Answer 10

tumor specific antigens

Question 11

What are these examples of:
mutated p53 tumor suppressor protein
unique Ig receptors on B cell lymphomas

Answer 11

tumor specific antigens

Question 12

What are these: over-expressed and abnormally expressed proteins

Answer 12

tumor associated antigens

Question 13

Give some examples of tumor associated antigens

Answer 13

MAGE in melanoma (usu only expressed in the testis and placenta)
HER 2 in breast cancer (epidermal growth factor receptor)
EGFR is expressed at a higher level on cancer cells

Question 14

5 antigens associated with myeloma

Answer 14

cyclin-dependent kinase 4
Beta-catenin
MAGE1
Tyrosinase
GP100/TRP2

Question 15

This antigen is seen in squamous cell carcinoma

Answer 15

caspase 8

Question 16

This antigen is seen in hepatoma

Answer 16

Alpha-fetoprotein

Question 17

This antigen is seen in Burkitt’s lymphoma

Answer 17

EBV

Question 18

Why are melanomas used for trials of anti-tumor immunity?

Answer 18

melanoma has 5 antigens, so it is easily recognizable

Question 19

What are the 5 cell types active in tumor immunity

Answer 19

CD8 T cell (responds to tumor Ags in MHCIs)
TH1 T helper cells (to activate macrophages)
activated macrophages (to kill or increase cytokines)
NK cells (for immunosurveillance and to kill tumor cells if they’ve lost their MHC expression later)
T regs

Question 20

What do NK cells do for tumors early on? Late in the game?

Answer 20

early: they are involved in immunosurveillance looking for whacky antigens
late: kill tumor cells if tumors lose MHCI

Question 21

If an NK cell encounters a tumor cell that does not have MHCI molecules on it, it cannot stimulate a negative signal. So, what happens?

Answer 21

NK cell will become activated, release its contents and kill the cell

**On-off balance favors “off”. Lack of MHC means no more “off” so NK cell stays “on” and kills.

Question 22

List three ways in which the tumor microenvironment reduces tumor immunity (killing of tumors)

Answer 22

1. low immunogenicity (no peptide:MHC ligand, no co-stimulatory molecules on tumor cells)
2. tumor is treated as self (tumor antigens are taken up and presented by APCs in absence of co-stimulation leading to tolerized T cells)
3. tumors induce immune suppression by secreting factors like IL-10 and TGF-beta which inhibit T cells directly

Question 23

What does CTLA-4 do for tumor cells?

Answer 23

it down-regulates T cell division

Question 24

What can persistent antigen presentation by tumor cells do to CTL’s?

Answer 24

cause immune exhaustion

Question 25

Immunotherapies for cancers can either be passive or enhance active immunity. What is the difference?

Answer 25

passive monoclonalAb: block growth factor receptors with an antibody
active immunity: increase immunity against tumor cells, adoptive transfer of CTLs, vaccines to boost immunity

Question 26

Herceptin, Erbitux, and Rituxan are all monoclonal antibodies used in immunotherapy against cancer cells. What is the major effective mechanism for these mAbs?

Answer 26

antibody dependent cell-mediated cytotoxicity

Question 27

chimeric monoclonal antibody used against CD20 in non-Hodgkins lymphoma

Answer 27

rituximab

Question 28

monoclonal anti-HER2 antibody used in breast cancer

Answer 28

Herceptin (trastuzumab)

Question 29

(blank), a receptor of the EGF receptor family, is expressed on both normal tissue and 20-30% of all breast carcinomas.

Answer 29

HER2

Question 30

What are 2 NEW means of manipulating the anti-tumor response?

Answer 30

1. anti-CTLA-4 to increase tumor-specific T cells

2. anti-programmed death receptor 1 to keep T helpers and CTLs alive and functioning

Question 31

Two mAbs used together to increase T cell activities?

Answer 31

ipilimumab + nivolumab (anti-CTLA4 and anti-PD1)

Question 32

How can you overcome anergy by tumor cells?

Answer 32

individual tumor cells can be transfected with B7 co-stimulatory molecules and used to re-stimulate T cells

Question 33

Tumors have tumor-specific antigens, but most tumors are weakly (blank).

Answer 33

immunogenic