tumor immunology Flashcards
carcinomas
arise from epithelial cells
most common form of cancer
sarcomas
arise from muscle cells, fat cells, or fibroblasts
lymphomas
solid tumors of lymphoid tissues
leukemias
derived from lymphocytes and other hematopoietic cells
benign tumors
slow growing
differentiated cells
encapsulated by CT–don’t spread
more concerning if in brain or heart
malignant tumors
undifferentiated cells
readily metastasize
usually fatal if untreated
immunosurveillance theory
immune system detects and destroys malignant cells before they grow into tumors
some believe we develop cancer daily but immune system lyses these cells
tumor specific antigens (TSAs)
unique to particular tumor not present on normal cells result of point mutations and gene rearrangements that occur during oncogenesis good target for treatment/therapy not often on human tumors
tumor associated antigens (TAAs)
shared by different tumors, also on normal cells
example: oncofetal antigens
large amounts of AFP –> liver cancers and cirrhosis
large mounts of CEA –> colon cancers and smokers
can be used to detect and monitor cancer progression
oncogenic viral antigens
some RNA and DNA viruses have been shown to induce tumors and express viral antigens on class I MHC
Epstein-Barr –> B cell lymphoma
HPV –> cervical carcinoma
hepatitis B –> hepatocellular carcinoma
RNA virus HTLV-1 –> T cell leukemia/lymphoma
relatively immunogenic
differentiation antigens
used to determine origin of tumor
not good for therapy target
why is it difficult for the immune system to respond to spontaneous tumors
rarely cause inflammation –> no costimulatory molecules
many tumors don’t express unique antigenic peptides
what cells are most effective against virus-induced tumors
CTLs
which cytokines enhance NK cell lysis of tumor cells
IFNs
TNF alpha
IL-2
lymphokine-activated killer (LAK) cells
enhance NK cell killing of tumor cell types
broaden tumor recognition capability
what type of tumor cells do NK cells kill
tumor cells of hematopoietic origin
virus-induced tumor cells
what mechanisms do macrophages use to kill tumor cells
ADCC
release of TNF alpha
TNF lyses tumor cells directly and causes hemorrhagic necrosis of tumor blood vessels
tumor evasion strategies
lack of expression of MHC –> no antigen presentation
state of tolerance to their antigens –> presented without costimulatory substances
“sneak through” –> small numbers not immunogenic –> then grow to larger numbers, mutate surface antigens
destruction of highly immunogenic variants
fast growth
anti-tumor antibodies act as blocking factors
masking of tumor antigens
TGF beta immunosuppression
encase selves in collagen/fibrin –> immunoprivileged site
non-immune cancer therapies
surgery
radiotherapy
hyperthermia
chemotherapy
advantages of immunotherapy
more effective against metastasis
tailored to tumor
fewer side effects
