L13: Tumor Immunology Flashcards
Tumor types
- ) Carcinomas: epithelial cells (most common CA)
- ) Sarcomas: muscle cells, fat cells or fibroblasts
- ) Lymphomas: solid tumors of lymphoid tissues
- ) Leukemias: lymphocytes and other hematopoietic cells
Characteristics of benign vs malignant tumors
- ) Benign: slow growth, differentiated cells, usually encapsulated, not fatal unless at critical site
- ) 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
- ) AFP: alpha fetal protein produced by certain liver CAs
- ) Oncofetal antigens: expressed on fetal, but not adult tissues
- ) 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
- S-100
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
- ) ADCC with some tumors (requires antibody)
- ) Downregulation of class I MHC in some tumors (which normally acts as inhibitory signal)
- ) 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?
- ) ADCC
- ) 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?
- ) Lack of MHC expression (particularly class I)
- ) Induce tolerance via absence of costimulatory molecules
- ) Failure to produce tumor antigen
- ) Anti-tumor abs acts as blocking factors
- ) Antigen shed by tumor cells
- ) Tumor antigens masked by mucopolysaccharides
- ) Tumor releases immunosuppressive substances – TGF-beta
- ) Creation of immunoprivileged site by encasement in collagen and fibrin
Types of immunotherapies available against tumors
- ) Tumor vaccines: vaccinate with tumor cells treated to increase immunogenicity or DCs loaded with tumor antigens. HBV vaccine decreases incidence of hepatocellular carcinoma
- ) Antibody therapies: lysis by ADCC/complement, abs against growth factors (Her2-neu – herceptin)
- ) Immunoconjugates: abs coupled to toxic substance directed towards tumor-specific antigen using Fab2 fragments
- ) Bi-specific antibodies: genetically engineering abs that recognize tumor antigens and immune system cells
- ) Purging bone marrow of tumor cells (autologous bone marrow transplantation in B cell lymphoma pts)
- ) LAK cell therapy: NK cells cultured in high levels of IL-2 – differentiate into LAK cells then reinfused back into pt
- ) TIL therapy: leukocytes from solid tumors cultured with IL-2 and given back to pt
- ) 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. 1.differentiation 2.oncogenic viral 3.tumor-associated 4.tumor-specific If an anti-idiotypic antibody was used to treat the lymphoma patient, it would recognize the \_\_\_\_\_ region of the tumor cell immunoglobulin? 1.Fab 2.Fc 3.Fc receptor 4.F(ab’)2
- tumor-specific
- Fab
What is the most dreaded, yet all-to-common, outcome of the treatment of B cell lymphoma with anti-idiotypic antibodies?
- Secondary tumors unrelated to the B cell lymphoma
- Neutralizing antibodies against the therapy antibody
- Tumor growth outpaces the amount of therapy antibody available
- Tumor variants that don’t bind the therapy antibody
- 4.
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?
- Dendritic cells
- Cytotoxic T cells
- Macrophages
- Natural killer cells
- 2.
A patient had a particularly aggressive cancer. A sample of the patient’s tumor revealed that the cells produced a large amount of IL-10. This likely provided a fair degree of protection from the immune system by shifting the patient immune response toward a _____ type of response.
- Th0
- Th1
- Th2
- Th3
- innate
- 2.
