Lecture 29 Flashcards
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multi hit hypothesis
clearly defined changes in cellular appearance occurs with neoplastic transformation
cell changes in carcinogenesis
what are the two major classes of tumor antigens?
tumor associated antigens
tumor specific antigens
Carcinoembryonic Ag (CEA)
Alpha fetoprotein (AFP)
CD20 and prostate specific Ag (PSA)
VEGF and MUC-1
name this antigen
Tumor associated antigens (TAA)
these are abnormal molecules that include mutated self molecules and foreign molecules
tumor specific antigens (TSA)
how are tumor antigens expressed?
TSA and TAA
markers that indicate cell physiology is alterd
can be cell associated or secreted (altered self cell and function of other cells)
what are the stages in tumor progression?
dysplasia
invasion
angiogenesis
metastasis
what are the three phases of the Cancer Immunoediting?
elimination or immunosurveillance
equilibrium
escape
these are the key players in tumor microenvironment?
discussed under elimination or immunosurveillance
NK, macs, CD8, cytolytic mechanisms like Fas/FasL, perforin/granzyme, IL-12, IFN-gamma
what is neoplastic growth equal to?
expression of new Ag and DAMPs
failure of elimination or immunosurveillance is equal to?
survival of tumor cells
what are the key players in equilibrium, adaptive response?
CD8 CTL, CD4 Th1, IFN-gamma, IL-12, cytotoxic mechanisms
what are the two examples of equilibrium?
immunoediting and cancer editing
how does escape occur, what two mechanisms?
immune evasion and immune suppression
what are the major mechanisms of tumor immunoevasion?
reducing MHC class I altering or turning off expression of immunogenic Ags shedding Ags masking Ags outpacing Ags (T cell exhaustion)
what are the major mechanisms of tumor immunosuppression?
produce immunosuppressive cytokines induce dysfunctional/tolerogenic DCs Differentiate MDSC Activate/recruit Treg cells Express FasL Express CTLA4 and PD1
what are the advantages of immunotherapy?
specificity target
limit therapy
generate memory immune responses
antibody and t cell based therapies are what types of immunotherapies?
passive immunotherapies
DC based therapies, tumor specific vaccines, cytokine therapy, and inhibitive immunosuppressive is what type of immunotherapy?
active immunotherapies
what is the goal of immunotherapy? how?
increase anti tumor response and inhibit immunosuppression
more targeted therapy
adoptive cell transfer
immunostimulation
changing the immune bias
what is the role for passive antibody immunotherapy?
targeted delivery of radio or chemotherapeutic agent
depletion of immunosuppressive cell subsets
receptor blockade
protein neutralization
what is the role of Tcell based immunotherapy?
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))
what is unique about the recombinant Chimeric Antigen Receptor (CAR)?
Fab fragment provides specificity
tail of CD3 provides activation
what is the role/advantage of DC based immunotherapies?
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
what is the goal of DC-based immunotherapies?
facilitate DC maturation and Ag processing to generate a DC that can rapidly and efficiently activate CD8 CTL
what are the counterstrategies for Treg activity?
deplete Treg cells
neutralize IL-10, TGF-beta, IDO
anti PD-1 or anti CTLA4 treatment
how do the immunotherapies work?
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
