Cancer immunology

what is cancer

uncontrolled proliferation of cells producing a tumour or neoplasm: can be benign or malignant

Difference between benign and malignant tumours?

Benign tumours do not invade or metastasise

malignant tumours are invasive and can metastasise

What are tumour antigens?

Antigens presented on MHC I by tumour cells that can be recognised by T cells.

Immunogenicity

The ability of a tumour to induce immune response

What determines tumour immunogenicity?

The level of tumour antigen expression, efficiency of MHC I presentation, and presence of co-stimulatory signals.

What are tumour-specific antigens (TSA)?

Unique antigens arising from mutations or viral infection, found only in tumour cells.

What are tumour-associated antigens (TAA)?

Normal self-proteins abnormally expressed or overexpressed in tumours (e.g. oncofetal antigens).

Example of an oncofetal antigen?

Alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA).

What is immunosurveillance?

The ability of the immune system to detect and eliminate tumour cells

Evidence for immune surveillance?

Increased cancer incidence in immunosuppressed patients: presence of tumour-infiltrating lymphocytes

What immune cells are involved in immunosurveillance?

NK cells, CD8⁺ cytotoxic T cells, macrophages, dendritic cells, and cytokines such as IFN-γ.

What are the three phases of cancer immunoediting?

Elimination —> Equilibrium —> Escape

How does immune-editing occur?

Immune pressure eliminates highly immunogenic tumour cells, allowing less immunogenic variants to survive and escape immune control.

What happens in the elimination phase?

Innate and adaptive immune cells destroy transformed tumour cells

What happens in equilibrium?

Tumour cells persist in a dormant state under immune control.

What happens in escape?

Tumours variants evade immune detection and grow uncontrollably

Role of NK cells in cancer immunity?

Kill tumour cells with low or absent MHC (missing self)

How do NK cells kill tumour cells?

Perforin-mediated pore formation and granzyme-induced apoptosis.

How does the innate immune system attack tumours?

NK cells induce apoptosis, macrophages release ROS and TNF-α, and cytokines promote inflammation and tumour destruction.

What is the “missing self” hypothesis?

NK cells detect and kill cells with reduced MHC I expression.

What are M1 macrophages?

Pro-inflammatory, anti-tumour macrophages associated with tumour regression.

What are M2 macrophages?

Immunosuppressive, pro-tumour macrophages that promote angiogenesis and tumour growth.

How might the immune system promote tumour growth?

Chronic inflammation, M2 macrophage activity, angiogenesis, tissue remodelling, and immunosuppression by Tregs.

Role of CD8⁺ cytotoxic T cells in cancer?

Recognise tumour antigens on MHC I and induce apoptosis of tumour cells.

Give three mechanisms by which the immune system attacks tumours.

CD8⁺ T-cell cytotoxicity, NK cell killing, macrophage-mediated destruction and cytokine-driven inflammation.

How do CTLs kill tumour cells?

Perforin–granzyme pathway and Fas–FasL interactions.

List mechanisms by which tumours evade immunity.

• Loss of tumour antigen expression

• Downregulation of MHC I

• Secretion of immunosuppressive cytokines (e.g. TGF-β, IL-10)

• Recruitment of Tregs

• Physical barriers (ECM)

How do tumours induce immune tolerance?

Antigen presentation without co-stimulation → T cell anergy or Treg induction.

What is monoclonal antibody therapy?

Passive antibody therapy targeting tumour antigens to induce ADCC or complement-mediated lysis.

What are immune checkpoint inhibitors?

Antibodies that block inhibitory receptors (e.g. PD-1, CTLA-4) to restore T cell function.

Give five examples of cancer immunotherapies.

Monoclonal antibodies, checkpoint inhibitors, CAR-T therapy, cancer vaccines, adoptive T-cell transfer.

Example of checkpoint molecules?

PD-1/PD-L1, CTLA-4.

What is CAR-T cell therapy?

Genetically engineered T cells expressing chimeric antigen receptors targeting tumour antigens.

Why is cancer immunology described as a “double-edged sword”?

The immune system can both suppress tumour growth and promote tumour progression via chronic inflammation.