Cancer Immunoediting

Question 1

What are the three phases of the cancer-immune system interaction described by the immunoediting hypothesis?

Answer 1

Elimination, Equilibrium and Escape

Question 2

Despite the immune system’s inherent defences, what evidence is there that neoplasms can circumvent such protection?

Answer 2

The increased prevalence of certain malignancies in immunosuppressed individuals, including organ transplant recipients and those with AIDS, points toward the immune system’s role in constraining cancer development

Question 3

Who is credited as one of the first to describe the possible role of the immune system in repressing cancer?

Answer 3

Paul Ehrlich

Question 4

What is the name of the concept, put forward by Burnet and Thomas in the 1950s-1960s, which describes the immune system’s ability to identify and eliminate malignant cells?

Answer 4

The Concept of Immunological Surveillance

Question 5

What did studies demonstrating the role of the immune system in rabbit skin graft rejection initially suggest about cancer treatment in early experimental models?

Answer 5

That it represented rejection of implanted tissue rather than cancer therapy

Question 6

What does a tumor require once it reaches a critical mass?

Answer 6

Angiogenesis and vascular proliferation

Question 7

What is the name given to the class of molecules released by necrotic and apoptotic tumor cells in the hypoxic tumor microenvironment?

Answer 7

Damage-Associated Molecular Patterns (DAMPs)

Question 8

What role do DAMPs play in the elimination phase of immunoediting?

Answer 8

They act as ligands for innate immune cells’ toll-like receptors and other germline-encoded danger ligand systems, leading to immune cell activation.

Question 9

What is the primary function of IFNγ in the elimination phase of immunoediting?

Answer 9

Direct antiproliferative tumor effect via the Stat1 pathway, as well as inducing the production of cytokines like CXCL9, CXCL10, and CXCL11, which further promote immune activation and limit angiogenesis

Question 10

What is the name of the family of antigens typically expressed solely in male germ cells, but found to be aberrantly expressed in some cancers?

Answer 10

The cancer/testis (CT) family of antigens

Question 11

Why are CT antigens not typically presented to T cells in male germ cells?

Answer 11

Male germ cells do not express HLA class I, which is necessary for antigen presentation to T cells

Question 12

What are neoantigens?

Answer 12

Novel tumour-specific antigens created by the translation of mutations located within gene exons.

Question 13

: What are “hot” tumors, and what is their prognosis?

Answer 13

“Hot” tumours are those with high immunogenicity, characterised by an abundance of tumour-infiltrating lymphocytes (TILs), and typically carry a more favourable prognosis.

Question 14

What did Koebel et al.’s research suggest about the role of the adaptive immune system in the equilibrium phase of immunoediting?

Answer 14

The adaptive immune system is involved in the equilibrium phase, evidenced by the equivalent tumour growth in mice treated with anti-CD4/CD8, anti-IFNγ, or anti-IL12p40 depleting antibodies

Question 15

What did Koebel et al. discover about the immunogenicity of tumors that grew late in wild-type mice?

Answer 15

They displayed diminished immunogenicity compared to those in Rag2− /− mice, but immunogenicity increased by maintaining the equilibrium phase with adaptive immune system-depleting antibodies

Question 16

How do some tumors limit the immune system’s ability to target them?

Answer 16

Some tumors can decrease or even lose expression of MHC class I molecules, preventing recognition by cytotoxic T lymphocytes (CTLs

Question 17

How do some tumor cells evade NK cell lysis?

Answer 17

Some tumour cells downregulate the expression of stress-induced ligands like MICA, which are typically recognised by activating receptors on NK cells, thereby evading NK cell lysis.

Question 18

What is the abscopal effect?

Answer 18

A phenomenon where localised radiation therapy leads to regression of unirradiated metastases distant from the primary irradiated site, often attributed to the stimulation of a systemic anti-tumour immune response

Question 19

What role does PD-1 play in the immune response, and how is it exploited in cancer immunotherapy?

Answer 19

PD-1 primarily suppresses differentiated effector T cells in peripheral tissues. Its ligands, PD-L1 and PD-L2, are often expressed on tumor cells and tumor-associated APCs. Checkpoint blockade therapies targeting PD-1 or PD-L1 aim to reinvigorate the suppressed T cell response against the tumor.

Question 20

How does activation of the CTLA-4 pathway decrease T cell effector function?

Answer 20

By trans-endocytosis of the CD80/CD86 ligands and inhibitory signaling that blocks proliferation and IL-2 secretion