Cancer & Immunotherapy Raja/Reza Flashcards
The tumor microenvironment is the ecosystem that surrounds a tumor inside the body. It includes immune cells, the ECM, blood vessels and other cells, like fibroblasts. The organization of different cell types in the tumor microenvironment may be different for each individual tumor, but different cancer types tend to have similar microenvironments. The microenvironment of many cancer types is very _______, or _______. This makes it more difficult for drugs to penetrate and reach the core of the tumor. The microenvironment surrounding many other cancer types tends to be more vascular, filled with blood vessels. In these cases, it may be easier for drugs to reach those cancer cells.
fibrotic, stiff
T/F: The tumor microenvironment is a unique environment that makes our cells difficult to combat the cancer
true
What do our cells release as a form of communication to other cells within tumor microenvironment?
Exosomes
Exosomes are vesicles that carry proteins out of the cell
Viruses can move inside of exosomes
There is a rapid growth in the cells and the nutrients change, which leads the cancer cells to undergo the ________ effect in the tumor microenvironment
Warburg
Environment is acidic and hypoxic
____________ and ____________ secrete VEGF to increase proliferation of blood vessels (which helps tumor to grow and divide)
Neutrophils, macrophages
The microenvironment changes biochemically to serve as a signal to call upon all the immune cells. Immune cells show up to combat whatever is foreign, but they get conflicting signals and it can make the immune cells change and ___________ tumor growth
promote
_______ cells detect abnormal tumor antigens expressed. The antigen has to be presented on MHC class I
CD8 T
Which T helper cell type is a part of the tumor microenvironment?
T helper 1 cell
B cells are found in the tumor microenvironment; however, recent studies have demonstrated that the presence and function of B cells are important during tumorigenesis. The antitumorigenic roles of B cells include….
hint: theres 3
1) antigen-presentation to T cells
2) anti-tumor antibody production
3) secretion of cytokines, like IFN-gamma, that promote cytotoxic immune responses
What are the tumor antagonizing immune cells?
Hint: theres 5
1) effector T cells
2) NK cells
3) DCs
4) macrophages (M1-polarized)
5) Neutrophils (N1-polarized)
What are the tumor promoting immune cells?
1) T reg
2) Myeloid derived suppressor cells (MDSCs)
_______________ cells are killing the target cells by granule exocytosis and FasL-mediated apoptosis, secreting IFN-gamma, and TNF-alpha to induce the cytotoxicity in cancer cells
effector T
________ cells patrol the bloodstream, seeking out virally infected host cells and tumor cells. They also release cytotoxic cytokines and are directly cytotoxic to cancer cells (IFN-y, TNF, IL6, GM-CSF, and CCL5). They are mediating the tumor killing response mainly through releasing perforin and granzymes to induce the apoptosis of the target cells.
NK
____________ cells present antigens and provide costimulatory signals for T cell activation. They suppress T cell functions in pro-tumor environments and promotes tumor growth. In anti-tumor environments, dendritic cells release cytotoxic cytokines and do antigen presentation to T cells
dendritic
The tumor microenvironment promotes the M2 phenotype through hypoxia and the secretion of cytokines (such as IL-4) to support tumor growth and progression. In anti-tumor environments, ______________ release cytotoxic cytokines and do antigen presentation to T cells. In pro-tumor environments, _________________ promote angiogenesis, tumor proliferation, chemotaxis, invasiveness, and metastasis. They are producing pro-inflammatory cytokines and ROS/nitrogen species for tumor cell killing
macrophages (M1-polarized), macrophages (M1-polarized)
As a tumor begins to grow, ______________ are recruited to the tumor microenvironment and promote inflammation through release of cytokines and ROS that promote tumor cell apoptosis. _____________ promote tumor growth through modification of the ECM. They are releasing the granules contains various antimicrobial and cytotoxic compounds to destroy malignant cells and secreting cytokines/chemokines to recruit other cells w/ anti-tumor activity.
neutrophils (N1-polarized), neutrophils (N1-polarized)
_______ cells are ubiquitous and promote tumor development and progression by dampening anti-tumor immune responses. They directly support the survival of cancer cells through the secretion of growth factors, and indirectly through interaction with stromal cells such as fibroblasts and endothelial cells.
T reg
In anti-tumor environment, _______ cells restore homeostasis to reduce chronic inflammation
T reg
In pro-tumor environment, ______ cells suppress anti-cancer immune responses and stimulate inflammatory cytokine production
T reg
In pro-tumor environments, _________ suppress T cell function and recruit immunosuppressive immune cells
myeloid derived suppressor cells (MDSCs)
__________ enhance angiogenesis and induce migration of cancer cells towards endothelial cells and promoting metastasis
Myeloid derived suppressor cells (MDSCs)
T cell (CD8+ and CD4+) directly lyses cancer cells and releases cytotoxic cytokines in an anti-tumor environment. However in a pro-tumor environment, they…..
release tumor promoting cytokines
The tumor evades anti-cancer immune responses by eliminating immunogenic antigens or maintaining cancer clones without cancer antigens so that they are not recognized by T cells. Basically they have fewer __________ antigens
immunogenic
The tumor avoids immune recognition by downregulating MHC class 1. Tumors that lose ___ MHC class I molecule might be able to avoid recognition by specific CD8 cytotoxic T cells while still remaining resistant to NK cells
1
The tumor avoids immune recognition by ________________, which are proteins produced by tumor cells that get into a cell and block the action of TAP1/2
immunoevasins
(blocks peptide entrance into the ER, and if there’s not enough MHC class 1, then the tumor is getting away with being there)
What is the function of TAP1/2?
TAP1/2 help load antigen on MHC class I
What is the enzyme that does most of the immunosuppression for immune cells (specifically T cells and NK cells) in the tumor microenvironment to help tumor grow?
IDO
What are the 5 textbook mechanisms by which tumors avoid immune recognition?
What are the 8 strategies used to target tumor microenvironment for cancer therapy?
What are some tumor specific or tumor recognition antigens?
Other ones not in table:
-TRA-1-60/ TRA-1-81 for carcinoma
-HER2 is the primary antigen in a lot of breast cancer cases, this is a good discovery in which researchers can use this as a marker and design a drug that has high efficacy for HER2 → drug = herceptin
Tumor cells are not supposed to have ______. So, PD will never bind and the T cell can then kill the tumor cells. This is because tumor cells upregulate ______ on their surface.
PDL, PDL
PDL binds to PD1 = putting the brakes on T cell → doesn’t get activated
Anti PDL antibodies → blocks PDL so that it cannot bind to PD1 → activated T cells for killing tumor cells
Chimeric antigen receptors (CARs) are fusion receptors that contain extracellular antigen-specific domains fused to intracellular domains that provide signals for activation and co-stimulation. These receptors are introduced into T cells via ________ vectors to produce CAR T cells. The antigen recognition domain is on CAR T-cells (which holds the fragment of an antibody specific for the antigen (the specific cancer the patient has))
retroviral
_____________ antibodies against tumor antigens, alone or linked to toxins, can control tumor growth
Monoclonal
What are some examples of tumor antigens that have been targeted by monoclonal antibodies in therapeutic trials?
