Lecture 16: Tumor Immunology Flashcards
True or False: One feature of cancer cells is that arise from a single cell (monoclonal origin)
True
- Therefore: all resulting daughter cells following division of parental cell are identical
True or False: Most tumor cells represent clonal progeny of a single aberrant cell
True
___ causes cell with damaged DNA to undergo apoptosis. Over 50% of cancers have a mutation in this gene.
p53
The main theory surrounding the field of tumor or cancer immunology is that mutations in genes, which result in neoplastic cells, also lead to changes in expressed ___
proteins
- changes protein SHOULD result in recognition of that protein as nonself antigen by immune system
Four pieces of evidence to support immune response to tumors?
1) Immunosuppressed people are more likely to develop tumors
2) CTL/NK cell deficient people have higher incidence of spontaneous tumor formation
3) Solid tumors contain lymphocytes and monocytes
3) Newly transplanted tumors are rejected at higher rate and more rapidly in animals that HAVE BEEN previously exposed to tumors of same type - anamnesic immune response
Which type of immunity is largely mediated by NK cells, which recognize lack or deficiency of self HLA on tumor cells>
Innate Immunity
Tumor cells may be lysed by __ and ___ antibody and complement
IgG and IgM
- however, this is harder if tumor is large or encapsulated in fibrous tissues
Tumor cells may be destroyed by phagocytes if they have been opsonized by __
IgG
True or False: Antibodies can neutralize spread of tumor cells by sterically interfering with tumor cells’ ability to adhere to surrounding tissues
True
In ADCC, ___ antigens induce antibodies (usually IgG) that bind to tumor cell
tumor
In ADCC, __ cell, possessing Fc receptors, attaches to tumor cell through antibody ___
K cell; antibody bridge
K cell is usually a ____
Natural Killer cell
When are substances released from the K cell?
When in close contact with tumor cell
What is the Fc receptor on K cells?
FC-gamma-RII (CD16)
CD8+ Cytotoxic T cells recognize tumor antigens through HLA Class __
HLA Class I
CTL activation is dependent upon Th1 cytokines, such as ___
IL-2
What is the single most important end-line defense mechanism against tumors?
A. CD4+ T cells
B. B cells
C. CD8+ T cells
C. CD8+ T cells
How do activated macrophages, as parts of the adaptive immune response, destroy tumor cells?
- Release lysosomal enzymes and TNF-alpha onto tumor cell surface
____ cells: make cytokines that activate macrophages, induce CD8+ CTL activity and upregulate HLA Class I (on tumor cells) and HLA class II (on antigen processing cells)
CD4+ T Helper Cells
What is the most important cytokine made by CD4+ T Helper cell? Why?
IFN-gamma
- attracts and activates macrophages to area of antigen, prevents emigration of macrophages away
- upregulates HLA Class 1/2
The production of which cytokine is key to activation of CTL and NK cells?
IL-2
True or False: If a tumor grows in an immunologically privileged site, the immune system may not be effective at eliminating it
True
Prostaglandins and Th1 inhibiting cytokine ___ could lead to anergy of infiltrating T cells
IL-10
___ can inhibit Th1 response, decreased NK activity, inhibit antigen uptake and presentation, and dampen the function of CD4+ and CD8+ T Lymphocytes
A. IL-10
B. CTL
C. TGF-B
C. TGF-B
Which two molecules on T cells is used to limit the amplitude and duration of immune response?
CTLA-4 and PD-1
- therefore: if a tumor expresses ligand for PD-1 (PD-L1) it can decrease activity of tumor specific T cells
Many believe that the tumor that survives immune surveillance and the initial immune response is the one that is least ___
antigenic
True or False: Blocking antibodies, which coat tumor cells, may prevent recognition of tumor cell by CTL
True
What are the three categories of immune therapy?
1) MAB to initiate an immune response
2) MAB to increase pre-existing IR
3) Immunomodulatory molecules to increase pre-existing immune response
4) Adoptive T cell transfer therapy
Monoclonal antibodies specific for surface molecules on tumor cells can be used to initiate tumor cells via ___, ___, and ___
ADCC, opsonization, and phagocytosis
___: anti-CD20 used to target B cells in B cell lymphomas
___: anti-EGFR used to target cancer cells in colorectal, head/neck cancer
Rituximab
Cetruximab
Monoclonal antibodies to increase existing pre-existing immune response is dominant by a class of molecules known as ____
checkpoint inhibitors
Will interactions between CD28 on T cell and CD80 or CD86 on the APC amplify or dampen responses?
Amplify
CTLA-4 interactions with CD80 or CD86 significantly decrease activation of which cells?
T cells
Administration of anti-CTLA-4 antibody blocks ability of CTLA-4 to become engaged on T cells by ___ or ___
CD80 or CD86
True or False: Anti-CTLA-4 agents results in enhances tumor specific CD4+ T cells and loss of T reg function in tumor microenviornment
True
____/____ interaction play a major role in limiting immune responses during infection and promoting maintenance of tolerance in periphery
PD-1/PD-L1
True or False: Activated T cells normally increase expression of PD-1 as part of normal immune response
True
True or False: T-regs express PD-1
True
What effect do mAbs that block PD-1/PD-L1 have on number/activity of Tregs at tumor site?
Decrease number and activity
Most successful adoptive T cell transfer to date?
CAR-T cells
Why is rejection not a concern in adoptive T cell transfer?
because tumor specific t cells are removed from patient, then activated and expanded, before being returned to the patient
Therapeutic Tumor Infiltrating Lymphocytes, a type of adoptive T cell transfer, has been successful in treating which cancer?
Melanoma
note: in this treatment, T cells are returned to site of tumor and kill remaining tumor
HPV vaccine is a prophylactic vaccine to prevent ______ _____
cervical carcinoma
Provide an example of a therapeutic or treatment vaccines:
Bacillus Calmetter-Guerine vaccine
- approved for bladder cancer
(note: therapeutic vaccines stimulate immune system to attack cancer cells)
