Cancer immune/tumor bio Flashcards
Know it, ya know
HTLV-1 can cause
T-cell leukemia/ lymphoma
Epstein Barr Virus can cause
Burkitt’s lymphoma
Hepatitis B virus can cause
Liver Cancer
Papillomavirus can cause
uterine cervix carcinoma
antigen expressed on tumor cells but not on normal cells
tumor-specific antigen
antigen expressed on tumor cells but also on normal cells
tumor-associated antigen
How do you generate tumor antigen?
gp 100 are cut out and spliced together in the protesosome and expressed in HLA-A32
How do NK cells and gamma-delta T cell work?
MICs are expressed and NK cells (NKG2D receptor) and GD T cells
How do tumor cells circumvent MIC detection?
Tumor cells secrete protease that cleave MIC, which bind to NKG2D receptor, so NK cells do not detect.
What does Tred do? especially in cancer?
Express TGF-Beta and IL-10, anti-inflam, controls adaptive system; favors tumor by suppressing T-Cell response
what does gemtuzumab do?
AML, Ab is endocytosed by the tumor cell and cleavage of the toxin, toxin breaks DNA, tumor specific response
What does anti-CD20 do?
After binding to B-cells, conjuagted to I131 and Indium 111, local radiation–damage the cells’s DNA–cell dead
What does limitless replicative potenial depend on?
Evading senecence, evade mitotic crisis, capacity for self-renewal.
Warburg effect?
using aerobic glycosis by upregulating GLUT1, intermediates are used for biosynthesis; Glucose hogging and (hypoxic condition) tumors glutamine hog (Krebs cycle)
What is Desmoplasia?
growth of stromal component of ECM, prominent in leading edge carcinoma
What cancer associated fibroblasts do?
initiation of tumor, EMT–metasis, angiogensis, sustain proliferation
What do cancer asscoiated adipocytes?
Release MMPs–migration and inflitration; use as energy source; pro-inflammatory cytokines
What do endothelial cells do in cancer?
angiogenic cells: leukocyte recuitment, tumor growth and metastasis; evade immunosurvailance and enhance chemoresistance
What is M1 macrophage associated with?
Differeniates by IFN gamma and LPS, and secretes Il-1, il-6, TNF-alpha)–important in immune defense, they are proinflammatory antimicrobial and tumoricidal; ROS tissue damage
What is M2 macrophage associated with?
differentiated by il-4, il-10, il-13; anti-inflammatory, wound healing, promote tumor growth
How to switch between M1 and M2?
Normoxia-M1 behavior then, hypoxia–M2 behavior
Which one more in tumor promotion, M1 Or M2?
M2 as promotes angiogensis, invasion/metastasis
Bottom line for macrophages in role cancer?
paracrine and autocrine signaling that enhance tumor properties
What is ECM role in cancer?
tumor cell bind to ECM via integrins–motility, synthesis, and ECM releases factors that are needed for induction and proliferation of neoplastic cells and angiogenesis
How does MMPs do in tumor cells?
proteolysis of substrates generate fragments that regulate pathways for invasion, angiogenesis, immune regulation, and metastasis
How does telomerase activity affect cancer cells?
Increase telomerase size –replicative immortality
What are MMPs?
Zinc and Ca dependent endopeptidases
1 step of tumor cell invasion
Loosen cancer cell-cell interact. and basement membrane interact. E-cadherins are low/lost (colon, breast, stomach)
2 step of tumor cell invasion
degrades ECM and BM (due to MMPs, Cathepsin D, plasminogen)
3 step of tumor cell invasion
Attachment to new ECM components: no integrins that bind to BM , and MMPs give new sites for the tumor to attach
4 step of tumor cell invasion
Invasion, propel themselves through degraded basement membrane and deeper ECM
How does a cancer cell move?
produce and release automotilty–bind to collagen and ECM to move, proteolytic fragments are chemotactic–cell moves forward
Well diff and mod diff cells move in:
collection as cell-cell interactions are maintained
poor diff and anaplastic cells move in
single cells
How does active intravasation of tumor cells
factors from tumor associated macro (TNF-alpha and chemokines), tumor cell follows
How does passive intravasation of tumor cells
increased vaso permeability, increased tumor interstitial pressure push tumor cells
How do tumor cells survive intravascularly?
cancer cells aggregate into clumps with RBC and platelets–enhance survival and enhance implantion to destination
What facilitates extravasation of tumor cells?
tumor releases TGF b and TNF-A, increase MMPs–so selectins on cancer cells and endothelial cells
What affects metastasis?
Anatomic, vascular drainage of primary tumor site, tropism of particular cancer for specific tissues
What metastaise to brain
lung, breast, melanoma, renal, colorectal
What metastaise to lung
renal, colorectal, melanoma, breast, sarcoma
What metastaise to liver
colorectal, pancreatic, breast (ER-), lung, stomach
What metastaise to bone
breast (ER+), lung, prostate, renal, colorectal
When does EMT occur normally
Embryonic morphogensis, wound healing
In Mesenchymal cells, which adhesive molecule is lost? What genes lead to this loss?
E-cadherins (Can also be cleaved by MMP3), SNAIL and TWIST
What protein is increased in mesenchymal phenotype?decreased?
intermediate filaments (vimentin) and smooth muscle actin increases; keratin decreases
What promotes EMT?
cross talk in tumor microenvrionment
