deck_21101974 Flashcards by Jorge Torres

How can the immune system control cancer?

Destroying viruses that are known to turn cells into cancer cells
Rapidly eliminating pathogens and regulating inflammation
Identifying and eliminating cancer

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How can we prove that the immune system controls cancer?

Immunodeficient individuals have an increased incidence of some types of tumors
Lymphocytic infiltrates around some tumors and enlargement of draining lymph nodes correlate with better prognosis
Tumor rejection shows features of adaptive immunity and is mediated by lymphocytes
Tumors evade immune surveillance in part by engaging inhibitory receptors on T cells

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An organism with a good immune system (adaptive and innate) is less likely to have tumors than an organism with problems in the either immune system. True or false?

True

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What is the relation of AIDS and cancer?

The organism tends to develop rarer types of cancers, because the cells inhibited/destroyed by AIDS would have been the ones that normally prevent these cancers.

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What are TILs and how do they help cancer?

They are Tumor-infiltrating lymphocytes and their presence correlates with survival in ovarian cancer patients. How exactly I do not know (the ppt doesn’t say)

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If you could pick one type of Lymphocytes to see next to your tumor, which would you pick?

Either Th1 or CD8+, as those have the better chance of leading to a good prognosis.

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You found lots of Th2 cells next to your tumor. How do you react?

https://i.ytimg.com/vi/JGkHrSa083U/maxresdefault.jpg

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You found lots of CD8 T cells next to your tumor. How do you react?

Hurray!

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CD8 T cells can eradicate tumors. True or false?

True. I think

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If I immunize a mouse against a type of tumor, if I inject it with the same type of tumor but from a different mouse, what is the expected outcome?

The tumor develops as normal

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CTL cells are the main effectors in antitumor responses, but CD4 cells are important as well. Why?

CD4 cells are important for priming and differentiation of CD8 cells into CTLs

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When a cancer cell dies, it releases DAMPs. Is this beneficial for the survival of the tumor?

No, because the DAMPs activate DCs, which pick up a tumor antigen, go to the lymph nodes, activate a tumor-antigen-specific CD8 T cell, which turns into a CTL, goes to the tumor, and kills the sons of bitches.

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Describe the 7 steps of cancer immunity cycle

Cancer cell death releases antigens
APCs pick up these antigens and present them
(Lymph nodes) T cells become primed and activated
T cells (now CTLs) travel to the tumor
CTLs exit the blood vessel and enter the tissue
CTLs recognize cancer
CTLs KILL cancer, releasing cancer death antigens

and the cycle repeats

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What is cross-presentation of tumor antigens?

It’s when an APC presents a tumor cell’s antigen to a CD8+ T cell

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T cells are able to recognize antigens expressed by genes exclusively expressed by tumors but not antigens encoded by the mutated form of a normal gene. True or false?

False. They can recognize both.

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Neoantigens are classified as Tumor-specific antigens. True or false?

True

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Tumor-specific antigens, as the name indicates, are only found in cancerous cells while tumor-associated antigens can be found both in cancerous and healthy cells. True or false?

True

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A neoantigen is an altered self protein expressed only by cancer cells. True or false?

False. It is also expressed by cells infected by viruses.

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There are two ways for a tumor to be detected by the immune system:
1. It either generates an altered version of a self protein
2. It expresses a protein from a different stage of development (for example, expression of an embryonic gene)
True or false?

False. It can also express an antigen expressed solely by tumors or overexpress a normal protein as well. So, 4 ways in total.

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Tumor antigens are presented in MHC I. True or false?

True

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How do tumors create a TME?

They change the phenotype of DCs
2, Altered DCs promote differentiation of anti-inflammatory Treg and Th2 cells.
Treg and Th2 cells promote differentiation and accumulation of M2 macrophages and myeloid-derived supressor cells.
These cells not only provide growth factors for tumor cells and tumor blood vessels, but they also prevent the action of antitumor CTLs and Th1 cells.

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Inflammation promotes malignant transformation of cells and cancer development. Tregs promote anti-inflammation.
As such, seeing a high frequency of Tregs within a tumor microenvironment is a good sigh. True or false?

False. The higher the frequency of Tregs, the less likely that a patient’s immune system will be able to effectively fight cancer.
Also while the inflammation part is true, tumors ironically prefer to promote anti inflammation, hence why they promote Treg and Th2 cell synthesis.

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Who are the good guys and the bad guys in the tumor microenvironment

Good guys:
CD8 T cells
Th1
NK cells
M1 Macrophages
Gamma Delta T

Bad guys:
Tregs
Th2
Myeloid derived supressor cells
M2 Macrophages

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TGF-Beta is an immunosuppressive cytokine. True or false?

True

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Tumors can inhibit T cell activation by producing inhibitory ligands; they cannot produce inhibitory cytokines. True or false?

False. They can do both.

What are the two ways a tumor cell cant evade the immune system by not even interacting with a T cell?

It can fail to produce an antigen, meaning a T cell won't be able to recognize it or It can lack the MHC for it to process an antigen, making the T cell unable to interact with it.

As a tumor evolves and grows, it tends to express less and less MHC I. True or false?

True

If all tumor cells manage to lose their MHC I, they become impossible to kill by the immune system. True or false?

False. While CTL cells become unable to kill it, they are now more susceptible to be killed by NK cells.

How do NK and gammadelta T cells identify tumors without MHC I?

The tumors express MIC proteins on their surface, which the cells' NKG2D receptors can bind to, and allows them to kill the tumor.

Tumors can evade being detected _____ and _____ cells by making a protease that cleaves ___, a surface protein expressed on tumor cells. This makes it so these cells can't _______________________________________, and the binding of ___ to the _______ receptor of these cells leads to endocytosis and degradation of the _____/______ complex.

NK and gammadelta T cells MIC be detected by NK and gammadelta T cells MIC, NKG2D MIC/NKG2D

How are AlfaBeta T cells and GammaDelta T cells related in the fight against cancer?

αβ T cells keep a watch on cancer cells that produce neoantigenic peptides presented in MHC molecules. If a cancer cell tries to counter this by down regulating MHC, it now becomes detected by γδ T cells, which use NK receptors instead of TCRs, to detect and fight the cancer.

Explain E3

1. Elimination - Cancer appears and gets fucked by every immune cell the body has to offer 2. Equilibrium - All the pisslow cancerrandoms cancers get killed and only the most well adapted cancer cells survive, which are the ones that best can evade the immune system or suppress its response. They cannot proliferate and spread because of the adaptive immune response. 3. Escape - One of the cancers evolves too well and gets an endgame mechanism: It either becomes immune to being killed or recruits a Treg to protect it.

What types of cancer therapy exist and how do they work?

Surgery: Removing a bulk of the cancer cells Radiation: Damaging DNA in cancer cells beyond repair, forcing them into apoptosis Chemotherapy: Damages rapidly dividing cells, forcing them into apoptosis Immunotherapy: Using anti-tumor producing cells to treat cancer

In antibody therapy, B lymphocytes are isolated from the blood or tumor infiltrate of a patient and are expanded by culture in IL-2 and are infused back into the patient. This treatment, often combined with systemic IL-2 administration, leads to tumor regression in some patients. True or false?

False in the sense that this isn't antibody therapy (It's adoptive cellular therapy) and it isn't the transfer of b lymphocytes, its just lymphocytes.

How does systemic cytokine therapy work against tumors?

It enhances T-cell proliferation/activation because of IL-2, it increases antigen presentation because of IFN-alfa, which ends up slowly pushing the TME towards a pro-inflammatory state

In antibody therapy, cancer neoantigens are the targets. The targets need to be scarce, easily accessible, and should be expressed homogeneously on the surface of every cell, including cancer cells. These antibodies eradicate tumors the same way microbes are eliminated. These including opsonization and phagocytosis, NK cell-mediated apoptosis, and activation of the complement system. The two types of antibodies used in these therapies are naked monoclonal antibodies (which are ab without modifications) and conjugated policlonal antibodies, in which antibodies are conjugated with toxins or radioactive compounds Correct the wrong information

The targets need to be ABUNDANT [...] expressed EXCLUSIVELY on the surface of cancer cells they DON'T do NK cell-mediated apoptosis and instead antibody-dependent cellular cytotoxicity (and the other 2) conjugated MONOCLONAL antibodies

Conjugated antibodies bound to radionuclide serve to reveal what areas the cancer is in. True or false?

False. Radiation kills the tumor cell and it's neighbors.

How do naked tumor-specific antibodies kill a tumor?

They bind to the tumor cell and recruit NK cells to kill the tumor.

Describe the structure of BiTEs and their function

They are two antibodies, one for CD3 (anti-CD3) and one for CD19 (anti-CD19) bound together with "duct tape" by the heavy chain. This way, they can bind to both T cells and tumor cells, forcing them to form synapses and become cytotoxic.

In CAR T cell therapy, Lymphocytes are taken from the sick host, genetically modified to produce CAR, and placed back into the patient. True or false?

True

In CAR T cell therapy, the T lymphocytes that now produce CAR are able to become active from the tumor antigen alone, without needing to go through the normal path to activate a T cell. True or false?

True

One of the advantages of CAR T cell therapy is that it works on many types of tumors. True or false?

False. It works against few tumors.

What happens in CAR T cell therapy if the cancer cell loses the antigen CAR is trained against?

It develops a resistance to the treatment.

Why must CAR T cell therapy be done alongside anti-inflammatory therapy?

Due to the risk of a cytokine storm, as many T cells respond to the target antigen.

Dendritic cell vaccination works by created DCs that already carry the tumor antigens, placing them back into the patient's body, and then letting them present the antigen to CD8 T cells, which will make them kill the tumor cells. True or false?

True

Oncolytic viruses are viruses that cause cells to behave like cancer cells. True or false?

False. These are viruses that specifically target cancer cells.

What are the two advantages of oncolytic viruses?

The natural lifecycle of a virus ends with the cell bursting (which is good because the cell bursting is a cancer cell) The death of the cell releases DAMPs which gets picked up by DC and activates T cells.

How does checkpoint blockade work?

It uses antibodies to block CTLA-4, which prevents the suppression or inhibition of CD4 T cells, allowing them to activate more CD8 T Cells This also means tumors cannot stop CD8 T cells from carrying out their destructive programming, as the antibodies also block PD-L1, which is a CTL's inhibitory ligand.

Blocking inhibitory receptors in T cells induces tumor regression. True or false?

True

Tumor mutation burden, TMB, is a measure of accumulated mutations in tumor genome during its evolution. True or false?

True

TMB and MI are receptors to be targeted in cancer immunotherapy. True or false?

False. They are predictors of tumor response to immunotherapy.

Immunoscore is a measurement used to evaluate the density and spatial distribution of ___ and ___ within a tumor.

CD3+ and CD8+ T cells.

A "Hot" tumor is related to a high immunoscore, means they are inflamed, and means they will respond well to immunotherapy (such as checkpoint blockade) True or false?

True

A "Cold" tumor is related to a low immunoscore, means they are not inflamed, and means they will respond well to immunotherapy (such as checkpoint blockade) True or false?

False. Cold tumors need a priming vaccine to turn them "hot". The priming vaccines probably contain cytokines that favor inflammation

A "Cold" tumor is related to a low immunoscore, means they are not inflamed, and means they won't respond well to immunotherapy (such as checkpoint blockade) True or false?

True

A "Hot" tumor is related to a high immunoscore, means they are inflamed, and means they won't respond well to immunotherapy (such as checkpoint blockade) True or false?

False. Hot tumors are already inflamed, and, as such, have strong pre-existing adaptive immunity.

Why is a single target approach to cancer treatment often a bad idea?

Because tumors can avoid treatments through multiple ways. If multiple treatments are used, there are less ways for the tumor to adapt.

Explain the combination of checkpoint inhibitors + vaccines

Vaccines prime tumor-specific T cells, while immune checkpoint inhibitors prevent inhibition of these cells.

Explain the combination of Checkpoint inhibitors + CAR-T cells

CAR-T cells become exhausted in TME. PD-L1 blockade may restore function and improve persistence

Explain the combination of Radiation + immunotherapy

Radiation induces immunogenic cell death, releasing DNA, RNA, tumor Ag and danger signals. This can convert “cold” tumors into “hot” tumors and synergize with ICI

deck_21101974 Flashcards

(60 cards)