Tumors Flashcards
development of blood supply
angiogenesis
metastasis
leave their site of origin to invade other tissue
spreading of cancer cells to distant sites, focus of new growth
Cancer cells characteristics
Stimulate their own growth
Ignore Growth inhibiting signals
They avoid death by apoptosis
Replicate continuously to expand their numbers
Evade or outrun the immune system
tumor, neoplasm
cells that are growing abnormally
malignant transformation
the process through which a cell becomes able to form a cancer
- this involves accumulation of multiple mutations in genes that regulate cell division and cell survival
adenoma
benign
adenocarcinoma
malignant
malignant vs benign
malignant is worse than benign
adenoma characterization
encapsulated, localized, and limited in size
adenocarcinoma characterization
not limited by capsule, invasive, can break through basal laminae and invade adjacent tissues
common sites for tumor development
where cells turnover happens a lot or fast
skin cancer
melanoma
lymph glands cancer
lymphoma
bone marrow cancer
leukemia
Causes of cancer
Environmental
Chemicals, radiation, virus
Mutagens, carcinogens, oncogenic virus.
Causes of cancer
genetics
Predisposition to malignancy can be conferred by mutations in certain gene
BRCA1/BRCA2
mutant forms of these tumor suppressor genes increase risk of breast cancer and ovarian cancer by 5 fivefold (60% vs. 12%)
proto-oncogenes
genes whose products positively regulate cell division
normal, needed - good…
progression from normal tissue to cancer
series of mutations is acquired
oncogenes
mutated versions of proto-oncogenes that contribute to malignant transformation
tumor suppressor genes
encode proteins that prevent unwanted proliferation of mutant cells
p53 - tumor suppressor gene
over 50% of human tumors have a mutation in p53.
Papilloma virus (DNA)
worts (benign)
cervical cancer
Hepatitis B virus (DNA)
liver cancer (hepatocellular carcinoma)
Epstein Barr virus (DNA)
cancer of B lymphocytes
Nasopharyngeal carcinoma
B cell lymphoproliferative disease
RNA virus that cause cancer
HTLV1 = T cell leukemia/lymphoma
HIV = Kaposi sarcoma
leukemia definition
cancer of immune system
lymphoma definition
cancers of the immune system involving solid lymphoid tumors
myeloma definition
cancers of the immune system involving bone marrow
Anti-tumor response: A case of autograft rejection
- Clonal origin, unregulated growth, develop due to spontaneous causes or induced mutations.
Mouse infected with chemical carcinogen induced tumor
Take tumor out, give the immune system time to recognize the induced tumor cells.
Tumor was put back into mouse –> No tumor growth
tumor growth happened in the
syngeneic mouse.
CD8T cell can eradicate tumor from the mouse
How can the immune system recognize tumors as dangerous and target them for removal?
tumor antigens
-tumor specific
- tumor associated
tumor specific antigens
antigens present on tumor cells, but not on “normal” cells
tumor associated antigens
antigens present on tumors, but also on normal cells (at lower expression) are called tumor associated cells
example of generation of tumor specific antigen
presentation of mutant peptide through MHC class I. mutant peptide is only found in mutagenic cells
example of tumor associated antigens
Embryonic genes - get re-expressed
over-expression of normal self protein.
Tumor specific antigens (TSAs)
Present on tumor cells, not on normal cells
Certain p53, was and B-catenin variants)
Products of oncogenic virus (EBV, HPV) –> none of these would be expressed by cells. only virally encoded antigens.
TTA
not necessarily unique to tumors
tumor specific post-translational modifications
MUC-1 abnormal glycolysation and localization
TTA over expressed by tumors
Her2-Neu (breast cancer)
MUC-1 TTA
abnormal glycosylation and localization
cancer/tesis antigens
TTA
Restricted to Gametogenic tissue (immunologically privileged) and cancer
cancer/testis antigen map to
chromosomes X (50%)
immunogenic in cancer patients
expression may be associated with tumor progression and with tumors of high metastatic potential
how immunogenic are tumors
chemically or radiation induced tumors, viral tumors, due to generation of self
not immunogenic tumors
spontaneous tumors
immune response against self antigen generally requires breaking
self tolerance
tumor evasion
T cells have to see antigen only presented by MHC on the surface of the cell.
down regulation MHC –>
down regulation of MHC become e
excellent targets for killing by NK cells
secreted tumor factors
IL10
TGF-beta
PGE-2
all decrease the potency of anti-tumor effector cells.
tumors- apoptotic destruction of T cells
FasL
TRAIL
IDO
Tumors down regulate
MHC
negative co-stimulation (tumor mediated immune suppression)
CTLA4/B7 interactions
PD1/PDL1 interactions
down regulation of MHC
Treg cells and tumors
suppress immune system.
Suppressive activity through IL10 and TGFbeta
Depletion of Tregs, through antiCD25, slowed the growth of transplantable tumors.
Innate immunity tumor
NK, macrophage, DC
Adpative immunity
CD4, CD8 T cells, more limited role for B cells
organ often transplanted
kidney
best possible match of do not and recipient
Blood type (1) , and MHC (2)
goal:
achieve histocompatibility at virtually every locus
alloantigen, alloreaction
immune responses directed against MHC that is different than self.
three major types of transplantation
blood transfusion
solid organ
bone marrow
transplant rejection for kidney - what happens
recipient T cell at against donor organ
graft versus host disease
BM is transplanted from donor to recipient. The recipient receives a new immune system and the T cells from the donor (BM) attacks the recipient
