L7: Cancer Immunology

What is the cancer-immunity cycle?

The cancer-immunity cycle describes the series of steps to activate the immune response against cancer: release of cancer cell antigens, cancer antigen presentation to dendritic cells (DCs), priming and activation of antigen-presenting cells (APCs) and T cells, trafficking of T cells to tumors, infiltration of T cells into tumors, recognition of cancer cells by T cells, and killing of cancer cells.

What are tumor-associated antigens (TAAs)?

TAAs are normal proteins or carbohydrates expressed abnormally in terms of concentration, location, or timing relative to their state in healthy and fully differentiated cells.

What are tumor-specific antigens (TSAs)?

TSAs are new macromolecules present in tumor cells but not in normal cells, provoking immune responses and located on tumor cell surfaces or within.

What is immune therapy?

Immune therapy involves treatments that enhance or manipulate the immune system to fight cancer, including antibody-based therapies, vaccines, and checkpoint inhibitors.

What are immune checkpoints?

Immune checkpoints are regulatory molecules on immune cells that can either inhibit or stimulate immune responses. Examples include CTLA-4 and PD-1.

What is the role of dendritic cells in the cancer-immunity cycle?

Dendritic cells present cancer antigens to T cells, leading to their activation and the initiation of an immune response against tumor cells.

Name the different types of cancer vaccines.

Cancer vaccines include pathogen-based vaccines, TAA/TSA-based vaccines, tumor cell-based vaccines, DNA vaccines, and dendritic cell-based vaccines.

What are conjugated antibody-based immune therapies?

Conjugated antibody-based therapies link monoclonal antibodies to toxins, drugs, or radioisotopes to target and destroy cancer cells.

What are limitations of peptide vaccines?

Weak immunogenicity of some antigens and variability in antigen presentation efficiency.

What is the structure of a CAR?

1. Extracellular antigen-binding domain

2. Transmembrane domain

3. Intracellular TCR signaling domain

4. Costimulatory domain (e.g., CD28)

What are the 4 conjugated antibody-based immunotherapy?

1. Immunotoxin and antibody-drug conjugate (ADC)

2. Antibody-directed enzyme/ pro-drug therapy (ADEPT)

3. Immunoradiaisotopes

4. Immunocytokines

What role does TGF-β play in immune evasion?

TGF-β inhibits T/NK cell function, suppresses antibody production, and promotes regulatory T-cell activity.

What are non-conjugated antibody-based immune therapies?

Non-conjugated antibody-based therapies use monoclonal antibodies to activate immune cells or block growth factors without directly delivering drugs or toxins.

What is CAR-T cell therapy?

CAR-T cell therapy involves genetically engineering T cells to express Chimeric Antigen Receptors (CARs) that recognize specific cancer cell surface proteins.

What are the drawbacks of TCR therapy?

Drawbacks of TCR therapy include cross-reaction leading to off-target killing, and ineffectiveness against solid tumors due to an immunosuppressive microenvironment.

What is the significance of PD-L1 expression in cancer treatment?

PD-L1 expression is upregulated on tumor cells in response to activated T cells; blocking PD-1 or PD-L1 helps enhance T cell infiltration and anti-tumor activity.

Name three types of TAAs and provide examples.

Wrong concentration: HER2 in breast cancer.

Wrong place: MAGE proteins (cancer-testis antigens) in melanoma.

Wrong time: CEA (embryonic antigen) in colon cancer.

How are TSAs generated?

Chromosomal translocations (fusion proteins), mutations, viral proteins (e.g., HPV), or abnormal transcription (e.g., pseudogenes).

How does CTLA-4 differ from PD-1 in function?

CTLA-4 competes with CD28 for B7 ligands on APCs, dampening early T-cell activation. PD-1 binds PD-L1 on tumors, inducing T-cell exhaustion/apoptosis.

What is ADEPT?

Antibody-directed enzyme/pro-drug therapy: An antibody-enzyme conjugate activates a prodrug into a cytotoxic drug at the tumor site.

What are drawbacks of CAR-T therapy?

Cytokine release syndrome, off-target B-cell depletion (e.g., anti-CD19), and tumor resistance via antigen loss (e.g., CD19-negative relapse).

How does abnormal tumor vasculature hinder immunity?

Disorganized capillaries block leukocyte infiltration, and hypoxia impairs immune cell function.

What is a dendritic cell-based vaccine?

DCs loaded with tumor antigens (via electroporation/phagocytosis) and activated with cytokines (e.g., IL-1β, TLR ligands) to prime T cells.