Flashcards in L13: Tumor Immunology Deck (23):
1.) Carcinomas: epithelial cells (most common CA)
2.) Sarcomas: muscle cells, fat cells or fibroblasts
3.) Lymphomas: solid tumors of lymphoid tissues
4.) Leukemias: lymphocytes and other hematopoietic cells
Characteristics of benign vs malignant tumors
1.) Benign: slow growth, differentiated cells, usually encapsulated, not fatal unless at critical site
2.) Malignant: undifferentiated cells, readily metastasize, usually fatal if untreated
TSA vs TAAs
- TSA: tumor specific antigens (only on CA cells) – not common
- TAA: tumor associated antigens (also on normal tissues)
Examples of TAAs
1.) AFP: alpha fetal protein produced by certain liver CAs
2.) Oncofetal antigens: expressed on fetal, but not adult tissues
3.) CEA: carcinoembryonic antigen is high in colon CA and smokers
Viral oncogenic antigens. Where are these presented?
1.) DNA viruses: EBV, HPV and HBV
2.) RNA viruses: HTLV (adult CD4+ T cell leukemia/lymphoma)
• presented on class I MHC
Antigen(s) specific for B cell leukemias and lymphomas
- CD10 and immunoglobulin
Antigen(s) specific for T cell leukemias and lymphomas
- IL-2 receptor (alpha chain), TCR, CD45R and CD4/8
Antigen(s) specific for melanomas
Antigen(s) specific for carcinomas
- epithelial derived tissue, therefore cytokeratins
Antibodies are the strongest form of immunity against tumors. True / False
- False, cell-mediated immunity is
What type of tumors are CTLs produced against?
- Carcinomas, sarcomas and virus-induced tumors
What are TIL’s?
- Tumor-infiltrating lymphocytes, which are mainly of CTL subtype that are found in solid tumors
What type of tumors are NK cells produced against?
- Tumors of hematopoietic origin and virus-induced
CTLs are the best defense against virus-induced tumors. True / False
- True. NK cells can also lyse these cells, but CTLs are the best
Mechanism of NK cells destroying tumor cells
1.) ADCC with some tumors (requires antibody)
2.) Downregulation of class I MHC in some tumors (which normally acts as inhibitory signal)
3.) LAK cells – subset of NK cells that are exposed to high levels of IL-2 and have T lymphocyte homology. They enhance killing of various tumor cells as well as recognize them better.
What cytokines enhance NK cells in their lysis of tumor cells?
- TNF-alpha, IL-2
Action of macrophage in killing tumor cells?
2.) Release of TNF-alpha (downstream effect on NK cells +…) directly lyses tumor cells (? Free radicals, hemorrhagic necrosis of tumor blood vessels?)
How do tumor cells attempt to evade the immune system?
1.) Lack of MHC expression (particularly class I)
2.) Induce tolerance via absence of costimulatory molecules
3.) Failure to produce tumor antigen
4.) Anti-tumor abs acts as blocking factors
5.) Antigen shed by tumor cells
6.) Tumor antigens masked by mucopolysaccharides
7.) Tumor releases immunosuppressive substances – TGF-beta
8.) Creation of immunoprivileged site by encasement in collagen and fibrin
Types of immunotherapies available against tumors
1.) Tumor vaccines: vaccinate with tumor cells treated to increase immunogenicity or DCs loaded with tumor antigens. HBV vaccine decreases incidence of hepatocellular carcinoma
2.) Antibody therapies: lysis by ADCC/complement, abs against growth factors (Her2-neu – herceptin)
3.) Immunoconjugates: abs coupled to toxic substance directed towards tumor-specific antigen using Fab2 fragments
4.) Bi-specific antibodies: genetically engineering abs that recognize tumor antigens and immune system cells
5.) Purging bone marrow of tumor cells (autologous bone marrow transplantation in B cell lymphoma pts)
6.) LAK cell therapy: NK cells cultured in high levels of IL-2 – differentiate into LAK cells then reinfused back into pt
7.) TIL therapy: leukocytes from solid tumors cultured with IL-2 and given back to pt
8.) Cytokine therapy
a.) IL-2: generates LAK cells, activates CTLs
b.) TNF-alpha: anti-tumor effects, but potential to develop septic shock
c.) IFN-alpha: increases NK cell activity and increases class I MHC expression on tumors
d.) Transfection of cytokine genes into pt tumor cells: immune stimulation locally instead of systemically
A patient is diagnosed with diffuse large B cell lymphoma. A specific therapy was used that targeted the surface immunoglobulin that was expressed by his tumor cells. The tumor cell immunoglobulin is a type of _______ antigen.
If an anti-idiotypic antibody was used to treat the lymphoma patient, it would recognize the _____ region of the tumor cell immunoglobulin?
What is the most dreaded, yet all-to-common, outcome of the treatment of B cell lymphoma with anti-idiotypic antibodies?
1.Secondary tumors unrelated to the B cell lymphoma
2.Neutralizing antibodies against the therapy antibody
3.Tumor growth outpaces the amount of therapy antibody available
4.Tumor variants that don’t bind the therapy antibody
In an experimental attempt to treat a patient with disseminated colon cancer, cancer cells were transfected with a gene that increased the expression of class I MHC molecules. Which component of the immune response likely would participate in killing of the tumor cells?
2.Cytotoxic T cells
4.Natural killer cells