Tumor Immunity Flashcards
What are the two main types of tumor antigens?
TSA: tumor-specific antigens
TAA: tumor-associated antigens
Which types of tumor antigens are tumor specific antigens?
Virus induced: cross reactive and immunotherapy should be applicable to all individuals infected with the cells
Chemical/physical carcinogen-induced : random mutations in affected cell causing AG differences - no cross protection
Which types of tumor antigens are tumor associated antigens?
Oncofetal Ag/Carcinoembryonic antigen (CEA): high concentration disappear at birth and return in colorectal cancer
Oncofetal Ag/alpha-fetoprotein: Also expresed in liver during inflammation, high in fetal/maternal, low in adults
What will tumor Ags activate when presented to to the naive cells by APCs?
T-cells
When observed histologically, lymphocytes can be viewed around tumors and lymph nodes enlarge. What does this mean?
Immune like lymphocyte proliferation responses against tumors inhibit tumor growth
If an immunodeficient individual has cancer what would you observe?
An increased incidence of certain types of tumors indicating the immune system protects against tumor growth
“immune surveillance”
What does diminished T-cell function mean to the immune response in tumors?
CD4+ T cells can’t secete cytokines that activate macrophages and CD8+ T cells
No CTL mediated tumor eradication
When a transplant is rejected by an animal previously exposed to a specific tumor what occurs?
Immunity tumor transplants can be transferred by lymphocytes from a tumor-bearing animal
Tumor rejection is mediated by lymphocytes
How do CD8+ T cells in the adaptive immune system respond to tumors?
Perform immune surveillance function recognizing and killing potentially malignant cells that express peptides derived from tumor antigens ad are presented with class I MCH
How do CD4+ T cells in the adaptive immune system respond to tumors?
Secrete IL-2 to activate CTLs and IFN-g to activate macrophages
How do antibodies in the adaptive immune system response to tumors?
Mediate antibody-dependent cell mediated cytotoxicity (ADCC) so Fc receptors-bearing macrophages or NK cells mediate killing
How does the NK cell respond to tumors in innate immunity?
Kills many tumor cell types, espeically with reduced class I MHC expression
ADCC and lysis
IL-12, IL-15 and IFNg inc killing
Lymphokine-activated killer (LAK) cells - IL-2
How does a macrophage respond to tumors in innate immunity?
M1: classically activated inhibit tumor growth via TNF inducing thrombosis in tumor vessels
How do tumors escape immune response?
Losing expression of Ags
Down regulating MHC-1
Producing immunosuppressive cytokines
Tumor arising in immunologically privileged site
How can tumor gene evade by failure to produce tumor antigen?
Antigen-loss variant of tumor cell
Causes the T-cell to be blind to the tumor cell
If a tumor cell lacks an MHC gene what occurs?
The T-cell cannot recognize it
If a tumor produced an immunosuppressive protein (inhibitory ligand PD-L1) what occurs?
T-cell action is inhibited
Tumor associated macrophages
M2: alternatively activated to promote tumors and spread of cancers by altering tissue micro-environment and suppressing T-cell responses
IL-10, prostoglandin E2, arginase, TGF-B and VEG-F
Regulatory T cells
Suppress T-cell response to tumors
Number of T-regs inc in tumor-bearing individuals and these cells are found in the cellular infiltrates of certain tumors
Myeloid-derived suppressor cells (MDSCs)
Suppress anti-tumor innate and T-cell response
How can tumors be eradicated by the same effector mechanisms used to eliminate microbes?
Opsonization and phagolysis, activation of complement system and ADCC
ex: Anti-CD20 in B cells lymphoma pts
What are some ways anti-tumor monoclonal antibodies and destroy tumors?
Eradicate tumors the same way as microbes
Use antibodies that can directly activate intrinsic apoptosis pathways in tumor cells
Which antibody is specific for oncogene product HER2/Neu?
mAB Herceptin
Elicits an immune effector mechanism and interferes with growth signaling functions of HER2/Neu
How can there be adoptive transfer of tumor-specific T cells?
Lymphoctes isolated from the blood or tumor infiltrate of a pt
Expanded by culture in IL-2
Infused back into pt
Tx often combine w/ systemic IL-2 admin - some tumor regression
What are some say to enhance tumor suppression responses?
Vaccinating with tumor cells transfected with genes encoding B7 costimulators or cytokine genes
Vaccinate with tumor-antigen presenting dendritic cell
Vaccinate w/ plasmids containing complementary DNAs encoding tumor antigens that are injected directly into pts or use direct transfer of dendritic cells