Tumor immunology

Question 1

What is immune surveillance theory?

Answer 1

True role of T cells to constantly monitor surface of body cells and destroy abnormal cells before mutant/possible malignant clone develops

Question 2

What evidence supports immune surveillance theory?

Answer 2

Immunodeficient/suppressed people have
1) high incidence of tumors

2) lymphocytes in tumors is good prognostic indicator
3) small percentage of tumors spontaneously regress

Question 3

What evidence against immune surveillance theory?

Answer 3

Immunodeficient/suppressed people
1) Do not get random sample of all tumors possible

2) nude mice (no thymus) have no increase in tumors

Question 4

What is immunoediting?

Answer 4

Immune system’s role in development of tumors

Question 5

3 parts of immunoediting- Elimination

Answer 5

Most cells init by mutagenic events recognized and stim by innate/adaptive immune sys

tumor cells exhibit metabolic abnormalities –> expression of DAMPs –> activate innate immunity

Question 6

3 parts of immunoediting- equilibrium

Answer 6

T cells enter tumor and in equal with tumor rather than destroying tumor (tumor and lymphocytes in equilbrium)

keeps tumor in latency until sudden drop in immune response or incr tumor cell mutations

Question 7

3 parts of immunoediting- Escape

Answer 7

Tumors escaping immune system

1) blocking factors
2) modification of tumor assoc antigens
3) production of immunosuppressive factors
4) reduced expression of MHC 1

Question 8

What are tumor associated antigens?

Answer 8

Antigens that are abnormally expressed or over expressed on tumor cells

Question 9

What are tumor rejection antigens

Answer 9

TAA recognized by immune system and lead to cell destruction

Question 10

TAA from viral gene products

Answer 10

Predictable and generalized based on infecting virus (cervical cancer TAA from HPV)

Question 11

TAA from mutant gene products

Answer 11

Tumor specific antigens

Random unpredictable mutations to cellular porteins

Question 12

TAA from normal gene products

Answer 12

Oncofetal antigens
Differnetiation antigens
Clonal antigens

Question 13

what are oncofetal antigens?

Answer 13

antigens made in normal fetal tissue re-expressed in adult blood with cancers (carcinoembryonic antigen in colon cancer pts)

Question 14

what are differentiation antigens

Answer 14

lineage specific antigens over expressed in tumors (HER-2 in breast/PSA in prostate)

Question 15

what are clonal antigens

Answer 15

TAA uniquely expressed by malignant cells (not normal cells) –> idiotypes of surface immunoglobulins/T cell receptors

Question 16

What is carcinoembryonic antigen?

Answer 16

Oncofetal antigen normally found in fetal tissue but re-expressed in adults with colon CA

Question 17

Should CEA be used as screening test?

Answer 17

NO because high likelihood of false positive

Question 18

Should CEA be used in diagnosing colon cancer?

Answer 18

Yes

also CEA levels used to determine efficacy of excision of tumor (0 = complete excision; rising = recurrence)

Question 19

Role of CTL in killing tumor cells

Answer 19

CTL = most importance in tumor resistance

1) activated in lymph node
2) clonal expansion and migrate to tumor
3) interact with TAA presented by MHC 1
4) induce apoptosis of Tumor cell
5) secrete IFN-g –> stim macrophages

Question 20

How do tumor cells escape immune system?

Answer 20

Reduced expression of MHC 1

Question 21

Role of NK cells in killing tumor cells

Answer 21

NK cells have receptor for stress marker on growth-dysregul cells and Fc for IgG on tumor cell

used to kill tumor cells that downregul MHC 1

Question 22

What is TIL

Answer 22

Cells taken from tumor of a patient

expanded in culture with IL-2

Question 23

Role of tumor infiltrating lymphocytes (TIL) in adoptive cellular transfer therapy

Answer 23

1) destroy pt’s immune system with radiation
to make room for expanded clone

Cells from tumor should have increased potential to fight tumor

Question 24

Discuss the role of PD-1 and CTLA-4 in regulating T cell (specifically CTL) activity, and the use of monoclonal blocking antibodies against these receptors to prevent CTL down-regulation in tumor patients

Answer 24

a

Question 25

Passive antibody therapy

Answer 25

Using monoclonal antibodies to treat tumors

Question 26

Characteristics of monoclonal antibodies to treat tumors

Answer 26

1) mAb to TAA that activates complement and leads to cell lysis/ADCC
2) mAb tagged with poison that destroys tumor
3) mAb to growth factors to inhib self-stim tumors

Question 27

Antibody/T cell therapy

Answer 27

2 coupled mAb (one against CD19 and one against CD3) binding T cells to B cell lymphoma cells to facilitate T cell destruction

Question 28

How does BCG treatment cause tumor regression? (1)

Answer 28

BCG = TB vaccine

1) Increases RE activity to incr production of macrophages to clear blocking factors from tumors cells –> incr immune ability to clear tumor cells

Question 29

How does BCG treatment cause tumor regression? (2)

Answer 29

Inject BCG into tumor causes delayed hypersensitivity reaction that kills tumors (melanoma/superficial bladder carcinoma)

Question 30

Adv/Disadv with monoclonal antibodies to treat cancer

Answer 30

Adv: selective to target TAA and growth factors of tumor cells

Disadv: Very expensive to develop and produce

Question 31

Role of CTLA-4 and PD-1

Answer 31

tumor cells express ligands to inhibit CTL response of T cells by binding CtLA-4 and PD-1

tumor cells fight back; checkpoint inhibitors are CTLA-4 and pD-1 –> downregulation of their cytotoxic activity