Lecture 29

Question 1

multi hit hypothesis

clearly defined changes in cellular appearance occurs with neoplastic transformation

Answer 1

cell changes in carcinogenesis

Question 2

what are the two major classes of tumor antigens?

Answer 2

tumor associated antigens

tumor specific antigens

Question 3

Carcinoembryonic Ag (CEA)
Alpha fetoprotein (AFP)
CD20 and prostate specific Ag (PSA)
VEGF and MUC-1

name this antigen

Answer 3

Tumor associated antigens (TAA)

Question 4

these are abnormal molecules that include mutated self molecules and foreign molecules

Answer 4

tumor specific antigens (TSA)

Question 5

how are tumor antigens expressed?

Answer 5

TSA and TAA
markers that indicate cell physiology is alterd
can be cell associated or secreted (altered self cell and function of other cells)

Question 6

what are the stages in tumor progression?

Answer 6

dysplasia
invasion
angiogenesis
metastasis

Question 7

what are the three phases of the Cancer Immunoediting?

Answer 7

elimination or immunosurveillance

equilibrium

escape

Question 8

these are the key players in tumor microenvironment?

discussed under elimination or immunosurveillance

Answer 8

NK, macs, CD8, cytolytic mechanisms like Fas/FasL, perforin/granzyme, IL-12, IFN-gamma

Question 9

what is neoplastic growth equal to?

Answer 9

expression of new Ag and DAMPs

Question 10

failure of elimination or immunosurveillance is equal to?

Answer 10

survival of tumor cells

Question 11

what are the key players in equilibrium, adaptive response?

Answer 11

CD8 CTL, CD4 Th1, IFN-gamma, IL-12, cytotoxic mechanisms

Question 12

what are the two examples of equilibrium?

Answer 12

immunoediting and cancer editing

Question 13

how does escape occur, what two mechanisms?

Answer 13

immune evasion and immune suppression

Question 14

what are the major mechanisms of tumor immunoevasion?

Answer 14

reducing MHC class I
altering or turning off expression of immunogenic Ags
shedding Ags
masking Ags
outpacing Ags (T cell exhaustion)

Question 15

what are the major mechanisms of tumor immunosuppression?

Answer 15

produce immunosuppressive cytokines
induce dysfunctional/tolerogenic DCs
Differentiate MDSC
Activate/recruit Treg cells
Express FasL
Express CTLA4 and PD1

Question 16

what are the advantages of immunotherapy?

Answer 16

specificity target
limit therapy
generate memory immune responses

Question 17

antibody and t cell based therapies are what types of immunotherapies?

Answer 17

passive immunotherapies

Question 18

DC based therapies, tumor specific vaccines, cytokine therapy, and inhibitive immunosuppressive is what type of immunotherapy?

Answer 18

active immunotherapies

Question 19

what is the goal of immunotherapy? how?

Answer 19

increase anti tumor response and inhibit immunosuppression

more targeted therapy
adoptive cell transfer
immunostimulation
changing the immune bias

Question 20

what is the role for passive antibody immunotherapy?

Answer 20

targeted delivery of radio or chemotherapeutic agent
depletion of immunosuppressive cell subsets
receptor blockade
protein neutralization

Question 21

what is the role of Tcell based immunotherapy?

Answer 21

in vivo t cell proliferation leading to protection and memory response

t cells isolated

recombinant or can be engineered (recombinant TCR and chimeric Ag receptor (CAR))

Question 22

what is unique about the recombinant Chimeric Antigen Receptor (CAR)?

Answer 22

Fab fragment provides specificity

tail of CD3 provides activation

Question 23

what is the role/advantage of DC based immunotherapies?

Answer 23

deliver tumor Ag in a context that increases immunogenicity

Drive DC differentiation
Increase MHC and CD80/86 expression
create optimal cytokine environment
deliver most immunogenic Ag

Question 24

what is the goal of DC-based immunotherapies?

Answer 24

facilitate DC maturation and Ag processing to generate a DC that can rapidly and efficiently activate CD8 CTL

Question 25

what are the counterstrategies for Treg activity?

Answer 25

deplete Treg cells
neutralize IL-10, TGF-beta, IDO
anti PD-1 or anti CTLA4 treatment

Question 26

how do the immunotherapies work?

Answer 26

increasing innate immunity
increasing T cell and NK cell activation
changing the tumor environment via immunosuppression cells
actively inducing tumor specific immunity
broader combinations of the above