11.2 Cancer and the Immune System

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Questions and Answers

What characterizes cancer at the cellular level?

Cells die more rapidly than they divide

Cells divide more rapidly than they die (correct)

Cells undergo mutations causing them to stop dividing

Cells lose their ability to respond to immune signals

Which type of immune cell can directly lyse tumor cells?

M2 macrophages

M1 macrophages

CD8+ T cells (correct)

NKT cells

What are tumor-specific antigens?

Antigens found in all normal cells

Antigens expressed only on tumor cells (correct)

Antigens that suppress immune responses

Antigens that lead to normal cell replication

How do M2 macrophages contribute to tumor progression?

By promoting tissue repair and remodeling Signup and view all the answers

What role do antibodies play in tumor immunity?

They mediate killing of tumor cells through complement activation Signup and view all the answers

What characteristic do tumor-associated antigens have?

They are found in both tumor and normal cells Signup and view all the answers

How might tumors evade the immune system?

By secreting TGF-β to suppress immune responses Signup and view all the answers

What is the primary role of NK cells in the immune response to tumors?

To directly kill tumor cells using cytotoxic granules Signup and view all the answers

What is the primary reason for the development of tumors in the body?

Increased cell division without corresponding cell death Signup and view all the answers

Which type of immune response involves the production of TNF-related apoptosis-inducing ligand?

Neutrophil activation Signup and view all the answers

What role do classically activated M1 macrophages play in relation to tumor cells?

Killing tumor cells through nitric oxide production Signup and view all the answers

How do NKT cells recognize tumor antigens?

Through non-classical MHC class I molecules Signup and view all the answers

What is a common characteristic of tumor-associated antigens?

They can be found on both tumor cells and normal cells. Signup and view all the answers

Which mechanism allows tumor cells to evade the immune system?

Secretion of indoleamine 2,3-dioxygenase by tumor-activated DCs Signup and view all the answers

Which immune cells are primarily responsible for mediating antibody-dependent cell-mediated cytotoxicity?

NK cells Signup and view all the answers

Which statement best describes the role of CD4+ T cells in anti-tumor immunity?

They activate macrophages through IFN-γ. Signup and view all the answers

What triggers the development of tumors in the body?

Increased rates of cell division and decreased rates of cell death Signup and view all the answers

Which type of immune mechanism is primarily involved in the direct destruction of tumor cells by producing nitric oxide?

M1 macrophages Signup and view all the answers

Which of the following statements about tumor-associated antigens is true?

They are expressed on tumor cells and also normal cells. Signup and view all the answers

What is the role of antibodies in fighting tumors?

They can activate complement to facilitate tumor cell destruction. Signup and view all the answers

Which cells are known to activate macrophages through the production of IFN-γ?

CD4+ T cells Signup and view all the answers

How do tumor cells manage to suppress host immune responses?

Through secretion of TGF-β and other immunosuppressive factors Signup and view all the answers

What is a primary function of neutrophils in response to tumors?

To produce TNF-related apoptosis-inducing ligand Signup and view all the answers

Which immune response is associated with NK cells binding to MICA and MICB on tumor cells?

Innate immune mechanism Signup and view all the answers

Study Notes

The Immune System and Cancer

Cancer results from imbalances in cell division and death rates
Tumors form when cells divide faster than they die
Development of tumors: Carcinogens, radiation, viral infections, chronic inflammation, and genetic mutations can cause cells to transform
Intrinsic tumor suppression mechanisms often eliminate early-stage tumors; however, some survive

Tumor Antigens

Tumor-specific antigens are only present on tumor cells
Tumor-associated antigens are found on both normal and tumor cells

Immune Response to Tumors

Innate Immune Mechanisms
- Neutrophils produce TNF-related apoptosis-inducing ligand (TRAIL), triggering apoptosis in tumor cells
- Natural Killer (NK) cells express NKG2D, which binds to MICA and MICB on tumor cells, initiating apoptosis.
Macrophages
- Classically activated M1 macrophages kill tumor cells
- Tumor cells may be recognized by damage-associated molecular patterns (DAMPs) released by dying tumor cells, activating macrophages.
- IFN-γ, produced by tumor-specific T cells, activates macrophages, triggering nitric oxide (NO) production to kill tumor cells.
- M2 macrophages promote tumor growth by secreting vascular endothelial growth factor (VEGF) and TGF-β
Adaptive Immune Mechanisms
- CD8+ T cells directly destroy tumor cells using perforins and granzymes
- CD4+ T cells activated by antigen-presenting cells (APCs) contribute to direct or indirect tumor destruction.
- IFN-γ, produced by CD4+ T cells, activates macrophages
- Natural Killer T (NKT) cells target tumor cells displaying non-classical MHC class I molecules
Antibodies
- Antibodies produced by tumor-bearing hosts can target tumor antigens, activating complement or mediating antibody-dependent cell-mediated cytotoxicity (ADCC)

Tumor Escape

Some tumors actively suppress host immune responses
TGF-β induces tumor cell proliferation and angiogenesis
TGF-β suppresses anti-tumor immune responses
Tumor-activated dendritic cells (DCs) secrete indoleamine 2,3-dioxygenase (IDO), inhibiting T cell proliferation
Tumor cells often secrete galectin-1, stimulating angiogenesis
Programmed cell death ligand 1 (PD-L1), secreted by tumor cells, slows immune responses

Mechanisms by which Tumors Escape T Cell Immune Defenses

Failure to produce tumor antigens
Loss of tumor antigens
Mutations in MHC genes/antigen processing pathways
Lack of T cell recognition
Secretion of immunosuppressive proteins
Expression of inhibitory cell surface proteins (e.g., PD-L1)

Equilibrium

Tumor cells can maintain a steady state without progressing
Tumor cells are not completely eliminated, nor do they fully proliferate

Tumor Immunoediting

Tumor cells under sustained immune pressure may be edited by the adaptive immune system
Tumor cells growing without an adaptive immune system remain immunogenic

Cancer Immunoediting

Cells undergoing transformation release danger signals, which trigger intrinsic tumor suppression.
Equilibrium (persistence and dormancy) occurs when the immune system and tumor cells reach a balance.
Escape (cancer progression) occurs when suppression mechanisms fail and tumors resume growth.

Immune Evasion

Failure to produce tumor antigens, loss of tumor antigens
Mutations in MHC genes or antigen processing genes
Lack of T cell recognition
Secretion of immunosuppressive proteins; expression of inhibitory cell surface proteins

Tumor Immunotherapy

Nonspecific immune stimulation (microbial products, cytokines)
Passive immunization (monoclonal antibodies)
Active immunization (chemically modified tumor cells, DNA vaccines, vaccines against oncogenic viruses)

Adoptive Transfer of In Vitro Activated Immune Cells

In vitro activated lymphocytes are transferred to the patient to fight tumor cells

T Cell Inhibitor Blockade

Blocking PD-L1/PD1 interactions on tumor cells enables T cell activation, leading to tumor cell destruction.

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Description

Explore the complex relationship between the immune system and cancer in this quiz. Understand how tumors form, the role of tumor antigens, and the innate immune mechanisms involved in responding to cancer cells. Test your knowledge on key concepts like tumor suppression, immune response, and the impact of various factors on tumor development.