Cancer Biology chapter 7 and 8

What does the tumor microenvironment involve?

1. CAFs
2. Vascular network
3. Various infiltrating cells

Which are the heterogeneous populations of the cancer cells?

1. Cancer cell clones
2. Cancer stem cells

Which are the factors that influence tumor heterogeneity?

1. Genomic instability
2. Clonal selection
3. CSC

What is the clonal selection?

Having successive mutations that confer survival/growth advantage.

Which are the characteristics of cancer stem cells?

1. Unlimited cell proliferation capacity
2. Asymmetric division

What kind of tumors are the ones with CSC?

Agressive and therapy-resistance

Which are CSC senescence biomarkers used to evaluate resistance to the treatment?

1. β-galactosidase activity
2. p53 level and nuclear localization

TRUE or FALSE: Cancer stem cells do not contribute to tumor heterogeneity.

False

In which part of the tumor formation are CSC formed?

Initiation

How is CSC’s maintenance and differentiation favored?

By cell senescence and inflammation.

How can CSC be used for cancer?

They can be used as biomarkers to predict relapse.

What are the steps of cancer immunoediting?

1. Elimination
2. Equilibrium
3. Escape

What is happening in the elimination step?

Detection and elimination of transforming cells by CD8.

What is happening in the equilibrium step?

Between tumor cells surviving elimination phase and immune system pressure clone emergency.

What is escape (cancer immunoeditting)?

Growth of less immunogenic tumor cell clones

What is TMB?

Tumor mutational burden (#of mutations found in cancer cells DNA)

What does it mean if the tumor has high TMB?

More likely to express immunogenic neoantigens that can be recognized by CD8

How the tumor cells lose immunogenicity?

1. Genetic and epigenetic changes
2. Tumor antigen loss
3. MHC-1 downregulation
4. High PD-L1 expression

How INF-γ is related to cancer?

INF-γ secreted by CD8 T stimulates PD-L1 expression by cancer cells

Which are the immumosuppressive molecules that regulatory T cells produce?

1. IL-2
2. Granzyme/Perforin
3. ATP to adenosine conversion
4. Immunosuppressive cytokine production
5. CTL-4 expression

What is the classification of the immune components of the tumor microenvironment?

1. Hot tumors
2. Cold tumors
3. Mutated tumors
4. Infiltrated tumors

What do infiltrated tumors do?

Attack TME

What do hot tumors do?

Support effector immune cells in the TME

What is PD-1?

Programmed cell death receptor 1 expressed by T cells

What is PD-L1?

Programmed cell death ligand 1 expressed by cancer cells

What do PD-1 and PD-L1 do?

Suppression of antitumor T cell activity

Which are the causes of metabolic stress?

1. Blood flux decrease
2. Nutritional and metabolic needs increasε

Which are the consequences of metabolic stress and cell’s adaptive responses?

Neo-angiogenesis

What are the steps for tumors recruitimg blood vessels?

Sprouting angiogensis→vaculogenesis→intussusception→vessel co-option→vascular mimicry→tumor stem cell to EC differentiation

Which molecules expressed highly during angiogenesis?

1. VEGF-A by CC
2. VEGFR-1 and VEGFR-2 by EC

What is MCT?

Mono-carboxylate transporter

Mention some metabolic enzymes.

1. Fmarate
2. Succinate
3. 2-hydroxyglutarate

Which are the characteristics of HIF-α?

1. Oxygen-sensitive factor
2. Inducible

Which are the characteristics of HIF-β?

AhR nuclear translocator and constitutive

Is hypoxia oxygen depedent?

Yes

MCT 1 and 4 isn’t highly upregulated in cancer

False

Which are the tumor promoting effects of lactate?

1. dampening of the immun response
2. activation of c-Mys via HIF-2α stabilization
3. Overexpression of TGF-β2 in CC
4. HDACs inhibition, epigentic modification, steafness

What is the role of GPR8 I?

It limits inflammation and causes innate immune cell inhibition.

→most is adipose tissue

→decrease cAMP (that downregulates hormone-depedent triglyceride lipase)