PART 3: Immunity and Tumor escaping mechanisms (2)

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Questions and Answers

Why does the tumor microenvironment (TME) become depleted of glucose?

Glucose transporters are inhibited.

Immune cells utilize all the glucose.

Tumor cells consume excessive glucose due to the Warburg Effect. (correct)

Tumor cells lack glycolytic enzymes.

What byproduct of glycolysis contributes to the acidity of the TME?

Lactic acid (correct)

Acetyl-CoA

Pyruvate

Carbon dioxide

How does acidity in the TME affect immune cells?

Enhances their cytotoxic activity

Impairs immune cell function and induces anergy (correct)

Promotes T-cell proliferation

Increases their glucose uptake

Why does hypoxia impair immune cell activity in the TME?

Immune cells rely primarily on aerobic metabolism. (C) Signup and view all the answers

Which molecule is upregulated by tumor cells to enhance glucose uptake?

GLUT1 (D) Signup and view all the answers

How does lactate accumulation in the TME benefit tumor cells?

Inhibits immune cell function by increasing acidity (A) Signup and view all the answers

What happens to immune cells in a glucose-depleted TME?

They enter an anergic state. (D) Signup and view all the answers

Which immune cells are most affected by the acidic and glucose-depleted TME?

Natural killer (NK) cells and effector T cells (A) Signup and view all the answers

How does the Warburg Effect give tumors a survival advantage?

Allows faster energy production, supporting rapid growth. (A) Signup and view all the answers

How do tumor cells convert fibroblasts into cancer-associated fibroblasts (CAFs)?

Through TGF-ß signaling (B) Signup and view all the answers

What is the main role of CAFs in the TME?

Building a collagen barrier around the tumor (C) Signup and view all the answers

What happens to CD4+ T cells in the presence of high TGF-β levels?

They convert into regulatory T cells (Tregs). (D) Signup and view all the answers

How do tumors manipulate macrophages in the TME?

Polarizing M1 macrophages into pro-tumoral M2 macrophages (D) Signup and view all the answers

What is the function of M2 macrophages in the TME?

Anti-inflammatory and tumor-promoting (B) Signup and view all the answers

What type of immune cells are most actively suppressed by Tregs in the TME?

Effector T cells (D) Signup and view all the answers

What is the primary function of Tregs in the tumor microenvironment?

Inhibit immune response and protect the tumor (C) Signup and view all the answers

Which cytokine promotes the conversion of macrophages to the M2 phenotype?

TGF-β (B) Signup and view all the answers

What role do CAFs play in immune evasion?

Prevent immune cell infiltration by creating physical barriers (B) Signup and view all the answers

Which type of T cell is most likely to lose function in the hypoxic TME?

CD8+ cytotoxic T cells (B) Signup and view all the answers

Study Notes

Tumor Microenvironment (TME) Depletion of Glucose

Tumor cells consume excessive glucose due to the Warburg Effect.
Immune cells utilize glucose.
Glucose transporters are not inhibited.

Glycolysis and TME Acidity

Lactic acid is a byproduct of glycolysis, contributing to TME acidity.
Carbon dioxide, Acetyl-CoA, and Pyruvate are not byproducts.

TME Acidity's Impact on Immune Cells

TME acidity impairs immune cell function and induces anergy.
TME acidity does not enhance cytotoxic activity, promote proliferation, or increase glucose uptake in immune cells.

Hypoxia and Immune Cell Activity

Hypoxia, a lack of oxygen, impairs immune cell activity in the TME primarily because immune cells rely on aerobic metabolism.
Hypoxia does not trigger T-cell proliferation, reduce lactate production, or enhance M2 macrophage polarization.

Glucose Uptake Upregulation

GLUT1 is a molecule upregulated by tumor cells to enhance glucose uptake.
CXCL12, VEGF, and IL-10 are not the primary molecule.

Lactate Accumulation's Benefit to Tumor Cells

Lactate accumulation in the TME inhibits immune cell function by increasing acidity.
Immune cell proliferation, oxygen levels in the tumor, and neutrophil activation are not benefits.

Immune Cell Response to Glucose-Depleted TME

Immune cells enter an anergic state in glucose-depleted TMEs.
They do not increase glycolysis, rely on fatty acid metabolism or undergo apoptosis.

Immune Cells Most Affected by Acidic and Glucose-Depleted TME

Regulatory T cells (Tregs) are most affected.

Warburg Effect Survival Advantage

The Warburg Effect allows for faster energy production in tumors, supporting rapid growth due to the production of more ATP per glucose molecule.

Tumor-Induced Fibroblast Conversion

Tumor cells convert fibroblasts into cancer-associated fibroblasts (CAFs) through TGF-β signaling.

Role of CAFs in TME

CAFs primarily build a collagen barrier around the tumor.

TGF-β Effect on CD4+ T Cells

High TGF-β levels convert CD4+ T cells into regulatory T cells (Tregs).

Tumor Manipulation of Macrophages

Tumors manipulate macrophages by polarizing them into pro-tumoral M2 macrophages.

Function of M2 Macrophages in TME

M2 macrophages have anti-inflammatory and tumor-promoting functions.

Immune Cell Suppression in TME

Regulatory T cells (Tregs) actively suppress effector T cells in the TME.

Treg Primary Function

Tregs primarily inhibit immune response to protect the tumor .

Cytokine Promoting M2 Macrophage Conversion

TGF-β promotes the conversion of macrophages to the M2 phenotype.

CAF Role in Immune Evasion

CAFs create physical barriers to prevent immune cell infiltration.

T Cell Type Most Vulnerable to Hypoxia

CD8+ cytotoxic T cells are most likely to lose function in a hypoxic TME.

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Description

This quiz explores the complex interactions within the tumor microenvironment (TME), focusing on glucose metabolism, acidity, and hypoxia's effects on immune cell function. Understand how TME conditions influence immune responses and the implications for cancer therapy. Test your knowledge on the mechanisms underlying tumor cell glucose uptake and immune cell impairment in the TME.