Tumor immunology Flashcards
What are carcinomas?
Turmors that arise from epithelial cells and are the most common of cancers
What are sarcomas?
Tumors that originate in muscle cells, fat cells or fibroblasts
What are lymphomas?
solid tumors of lymphoid tissues
What are leukemias?
Tumors derived from lymphocytes and other hematopoietic cells
What are the characteristics of benign tumors?
relatively slow growth rate, consist of somewhat differentiated cells and usually become encapsulated by connective tissue, therefore they don’t spread to other body sites
When are benign tumors fatal?
They are not usually fatal unless they occur at critical sites such as the brain or heart.
What are the characteristics of malignant tumors?
consist of undifferentiated cells and readily metastasize. Cancer is usually fatal if untreated
What are tumor specific antigens? How do they arise?
antigens that are unique to a particular tumor and are not present on normal cell types. They arise as a result of point mutations or gene rearrangements that occur during oncogenesis.
Why aren’t TSAs used for drug therapy?
not commonly seen in human tumors
What are Tumor-associated antigens (TAA’s)?
antigens shared by different tumors and can also be found on normal tissues.
What is the immunosurveillance theory?
Immune system detects and destroys CA (daily?)
What are oncofetal antigens?
Antigens expressed on fetal, but not adult tissues
What are alpha fetal proteins?
Proteins produced by certain liver CAs, replaced by albumin in adult.
What are carcinoembryonic antigens?
Antigens that are increased in colon CA and smoking
What are tumor associated antigens useful for, if you cannot use them to target therapy?
Diagnostic and monitoring
What are the three DNA viruses discussed in class that have been shown to induce tumors and express viral antigens on class I MHC proteins?
Epstein-barr causes B cell lymphoma
HPV-cervical carcinoma
Hep B-hepatocellular carcinoma
What is the RNA virus discussed in class that can produce tumors?
The RNA virus human T lymphotropic virus-1 (HTLV-1) causes an adult T cell leukemia/lymphoma of CD4+ T cells.
Why are tumors derived from viruses particularly immunogenic?
Seen as foreign
What are differentiation antigens?
Tissue specific, or differentiation, antigens that are present on normal cells types of adults can be expressed by some tumor types that develop from a particular tissue
When are differentiation antigens used?
diagnosing certain tumors by revealing their origin
Why are tumors difficult for the immune system to respond to? (2)
Rarely cause inflammation
Don’t express unique antigens
How can antibodies contribute to tumor cell proliferation?
Block receptor sites for CTLs
True or false: antiboddy production has been demonstrated to inhibit tumor developement
False
CTLs are produced against what types of CA? (3)
carcinomas and sarcomas as well as virus-induced tumors.
What are tumor-infiltrating lymphoctytes largely composed of?
CTLs
NK cells are better at lysing CA cells with what origin?
Of hematopoeitic or virus induced
What is the mechaism that allows NK cells to attack tumor cells?
Downregulation of class I MHC
What are the three chemicals that cause NK cells to become LAK cells?
Interferons, TNF-alpha, and IL-2
How do macrophages attack tumor cells?
Release TNF-alpha which kills tumors, or attacks blood supply
ADCC
What are the tumor evasion strategies?
Down regulate MHC
Induce tolerance of specific T cells d/t lack of inflammation
How does the destruction of highly immunogenic tumor cells by the immune system lead to CA?
May just select out the easy ones and leave the less immunogenic CA
Can CA cells outgrow the immune system?
Yes
What can some antigens that are shed by tumor cells do?
bind to cell surface receptors of immune system cells and prevent proper function.
What is the effect of mucoploysaccharides on tumor cells?
Tumor antigens may be masked by tumor cell mucopolysaccharides which prevent recognition by the immune system.
What happens when TGF-beta is released by tumor cells?
Suppress immune system
How can tumor cells become immunoprivielged sites?
Encase themselves in collagen and fibrin
How does hyperthermia work to destroy tumors?
Superheat them
How does radiotherapy work?
X-rays or colbalt 60 induces ionizing radiation to destroy rapidly dividing cells
How does chemotherapy work?
Inhibits DNA replication, RNA transcription or protein syntehsis
What are the three advantages of tumor immunotherapy?
- Specificity to tumor cells
- Fewer side effects
- More effective
How can one vaccinate against a tumor?
Increase immunogenicity of tumor antigens to get an immune response
What are the MAGE antigens in melanoma prevention do?
Induce CTLs for melanoma
Why is the hep B vaccine considered tumor prevention?
It decrease the incidence of hepatocellular carcinoma.
What does Herceptin target?
HER-2/neu receptors of breast CA, to block ligand interaction
What are immunoconjugates?
Antibodies coupled to a toxic substance
What is the main issue with immunoconjugaes?
Cross reactivity
What fragments of antibodies are used in immunoconjugates to avoid non-specific binding?
F(ab’)2 (so no Fc binding)
How are bi-specific antibodies used in immunoconjugate therapy?
binds tumor antigens to CTLs
What is in vitro purging of bone marrow?
Freeing bone marrow from CA tumors via antibodies and complement to provide for bone marrow transplants
What is LAK therapy?
Peripheral NK cells cultured in high dose IL-2 to stimulate LAK cells. Lak cells are tumoricidal
What are the two CA types that LAK therapy has been effective in?
Renal cell carcinoma
Malignant melanoma
What is tumor infiltrating lymphocyte (TIL) therapy?
Leukocytes from solid tumors cultured with IL-2 and given to pt, thus giving pt LAK cells and tumor specific CTLs
What is cytokine therapy? Why is it not used more often?
IL-2 of INF-alpha is infused into patients to generate LAK cells and activate CTL’s in vivo.
Lots of side effects
What is the effect of administering IFN-alpha to pts? (3)
antiproliferative effects on tumor cells, increases NK cell activity, and induces class I MHC expression on tumor cells to make the tumors more immunogenic.
What is transfection of cyotokines genes into tumor cells?
Administering IL-2 or TNF directly to tumor cells via antibody targeting
