cancer immunology
innate immunity cells
NK, macrophages, dendritic cells, neutrophils, eosinophils, basophils
how does cancer suppress the immune system? secreting TGF-B cells stimulating Treg cells secreting IL-10 all of the above
all of the above
herceptin
anti-HER2, breat cancer
keytruda
anti-PD-1 -- approved against non-small-cell lung cancer (NSCL)
avastin
anti-VEGF -- DEC angiogenesis
M1 macrophages
anti-tumor cells that release reactive oxygen species and cytotoxins towards cancer cells can recruit other immune cells by releasing certain cytokines
acquired immunity
antigen specific and adaptive THINK: what is the threat and how can we recognize it?
how do cancer cells use PD-L1 to weaken cytotoxic response?
bind of PD-L1 to PD-1 activates SHP-2 phosphatase --> inactivates P13K pathways w/in T cell and DEC its own survival mechanisms
keytruda
block PD-1 checkpoint
Yervoy
blocks CTLA4 checkpoint
epstien-barr virus
burkitt's lymphoma
indirect exhaustion
cancer cells DEC antigen expression / masking with CAR itself
human papillomavirus
cervical cancer
dendritic cells -- antigen presenting cell (APC)
communication expert of immune system; identify pathogen at source and keep antigens for reference
cytotoxic T cell (CD8+)
cytotoxic --> bind target cells displaying (Ag+MHCI) complex --> destroy TCR recognizes (Ag+MHCI)
CD8+ cells
cytotoxic! assassins that respond to antigens displayed by MHC1 carrying cells --> seek out target --> destroy it head-on via FAS activation, perforin, granzyme B
CAR T cell exhaustion types
direct, indirect, self-imposed
immunoediting
disguise themselves as healthy cells via remove TATAs and TSTAs and MHC
many tumor cells and viral-infected cells ____ have MHCI
do not --> trying to evade T-cell response
macrophages
engulf pathogens and aid initial immune response (antigen presentation and inflammation); go from monocytes --> macrophages
helper T cell (CD4+)
enhances B cells, CD8+ t cells, macrophages, NK cells TCR recognizes (Ag+MCHII)
oncolytic viruses
ex. T-VEC oncolytic virus deviated from herpes for melanoma; infect cancer cells (no mechanism to eliminate virus) --> lyse cancer cells --> releases viral and antigens for identification of immune system
provenge
first FDA approved vaccine against metastatic prostate cancer; patient APCs removed, activated with tumor antigens (pap and GM-CSF), then reinjected
antigen presentation
foreign protein is phgocytosed --> enters cell --> proteases cleave the foreign protein --> preserve Ag peptides --> cleaved peptides are loaded onto MHCI and MHCII on cell surface
plasma cells
front-line defenders release antibodies into the bloodstream, making pathogens their place
CD4+ cells
helpers! support cells that respond to antigens displayed by MHC-2 carrying cells and assist B cells, NKs, and macrophages in their duties
how do cancer cells compensate for down-regulating MHC1 after stress response?
inhibit stressor production or secreting them as decoy
memory cells
keep knowledge of antigens for future infections
cell expresses MHC I and MHC II --> kill or no kill?
kill
cell expresses only MHC II --> kill or no kill?
kill
what do Treg NORMALLY help to prevent?
prevent autoimmune responses, but cancer turns them against the entire immune system
how do cancer cells use CTLA-4 to counteract B7 ligand and CD28 receptor?
priming action inhibited by binding of B7 to CTLA-4 --> keeps T cells in their inactive state --> CTLA-4 normally used for immune regulation and DEC activity post-infection, but cancer cells exploit --> avoid destruction
activation of M2 can lead to ...
production of growth factors, angiogenesis, immunosuppression, invasion and metastasis
natural killer cells
rapidly attack pathogens while keeping self-cells safe (self-cells are deactivated via presentation of MHC1 and lack of stress molecules)
direct exhaustion
secretory of inhibitory molecules, Treg activation, and/or INC PD-L1
T cells require 2 signals to be fully activated
signal 1: TCR on T cell binds (Ag + MHCI or II) signal 2: B7 (APC) binds CD28 (T cell)
what does releasing Il-10 and TGF-B cell do?
stimulates Treg
which cancer type is associated with a virus? burkitt's lymphoma liver cancer cervical cancer stomach cancer
stomach cancer
stomach cancer is associated with a _____ called ____ and causes ____ which create cancer which create cancer after many iterations of injury and reconstruction of the stomach
stomach cancer is associated with a bacteria called H.Pylori and causes ulcers which create cancer after many iterations of injury and reconstruction of the stomach
What INC a patient's chance at 5-yr survival?
the more tumor-infiltrating lymphocytes (TILs) a patient has
which cells suppress MHC 1 expression?
viral-infected cells and tumor cells to evade t cell activation
acquired immunity cells
B cells, T cells, and their variations
after primary response ____ recall certain antigens for the ____ response if you get infected again
B cells; secondary
chimeric antigen receptor T cells
CAR-T cells genetically modified to better target cancer
self-imposed exhaustion
CAR-Ts competing with endogenous T cells for tumor antigen binding
which cells can be destroyed by HIV?
CD4+
what cells can't detect MHC1 if it is removed?
CD8+ and MHC1 can't detect therefore no immune response
what types of cells express MHC 1
all healthy and normal cells
what does Treg do after cancer recruits it?
DEC activity of CD8+ and CD4+ cells --> protecting cancer cells therefore INC [Treg] --> lower chances of survival
don't kill me, i'll kill you
INC IAPs and DEC FAS activity to prevent apoptosis from occurring --> release FAS ligand (soluble or in vesicles) to trigger apoptosis in immune cells --> to debuff lymphocytes and kill them they will release inhibitory cytokines IL-10 and TGF-B --> stimulates Treg
patients suffering from AIDS/autoimmune conditions are more susceptible to their associated cancers. which is the most common arising cancer for these individuals? what virus is it associated with?
Kaposi's sarcoma -- associated with herpesvirus
tumor cells tend to down-regulate ...
MHC 1, which are overlooked in favor of pro-mitotic, anti-apoptotic up-regulation --> leaves them vulnerable to NKC attacks and MICA (after stress response)
why does every cell present MHC I?
MHC I integral for T cell activation and for NK cells
inhibitory ligand
MHC class I --> NK cell wont kill normal, healthy cells express MHC I
activatory ligand
MHC class II presence of BOTH MHC I and MHC II --> activatory overrides inhibitory --> NK kills stressed cells express MHC II
which cells are part of the innate immune system? Macrophages Dendritic cells B cells T cells
Macrophages Dendritic cells
T cell immune checkpoint: PD-L1
PD-1 receptor on T cell interaction with PD-L1 receptor on tumor cell
what do pericytes help improve?
Pericytes improve survival and completion of survival of endothelial cells (EC)
T cell task
T cell receives intel from APCs in the form of tumor-specific antigens --> T cells seek out tumor cells and destroy them --> cellular remains harvested by other immune cells for antigen collection --> checkpoint one
MHC 1 expression is critical to the activation of which cell?
T cells
how does CAR-T cell therapy work?
T cells from patient modified via Lentivirus --> express antibody fragments (scFv) and T cell activation domains (CD3zeta) --> does NOT need MHCs to bind to bind to cancer cells --> takes immunoedited cells off guard
T cell immune checkpoint: CLTA-4
T cells must bind APCs by both MHCs and B7 ligand (detected by Ts CD28 receptor) to continue
M2 macrophages
TAMs -- pro-tumor cells that have been transformed by tumor cells to act in their favor, releasing hallmark-stimulating cytokines
because of the viruses that may be associated with certain cancers, is the immune system better prepared for it?
Yes, because the immune system is already on high alert from the pathogen presence
hepatitis B virus
liver cancer
inhibitory ligand for NK cells?
mhc 1
activatory ligand for NK cells? will nk cells kill?
mhc 2, yes
will NK cells kill cells with MHC 1? why?
no bc MHC 1 is an inhibitory ligand
cell expresses only MHC I --> kill or no kill?
no kill
innate immunity
not antigen specific but responds immediately to infection, inflammation, cellular damage THNK: is this a threat or not?
Rituxan
one of first antibodies developed - non hogkins lymphoma
B cells
originate in Bone marrow -- responsible for humoral (blood soluble) immunity
T cells
originate in Thymus gland -- responsible for cellular (binding) immunity
immunotherapy promotes _____ immunity
passive immunotherapy