Tumor immunology, cancer immunotherapy

Question 1

Tumor suppressor genes

Answer 1

Genes that encode proteins that inhibit excessive cell proliferation or promotes apoptosis

Question 2

Oncogene

Answer 2

Cancer-inducing gene. Encode proteins that promotes cell survival or cell proliferation. Gain of function leads to cancer. Originates from a proto- oncogene.

Question 3

Conversion from a proto-oncogene to an oncogene:

Answer 3

An increase in protein activity due to activating mutation within a proto-oncogene
* change in the protein structure (e.g. RAS)

Question 4

Cancer immunosurveillance

Answer 4

The immune system can specifically identify and eliminate tumor cells on the basis of their expression of tumor-specific/tumor-associated antigens or molecules induced by cellular stress –>
The immune system identifies cancerous and/or precancerous cells and eliminates them before they can cause harm

Question 5

Tumor-specific antigens (TSA)

Answer 5

Unique to tumor cells, not found on normal cells
* Encoded by mutations in tumor cells that generate altered cellular proteins (neoantigen)
* Encoded by genes exclusively expressed by tumor cells (viral derived)

Question 6

Tumor-associated antigens (TAA)

Answer 6

Also found on normal cells but:
* Normally expressed at extremely low levels (overexpressed in tumor cells)
* Normally expressed only during fetal development (when the immune system is
immature)
* Stress related proteins

Question 7

Cancer immunoediting

Answer 7

A process whereby the interaction of tumor cells with the immune system generates tumor variants with altered immunogenicity

Question 8

Immunoediting is divided into three phases:

Answer 8

Elimination, Equilibrium and Escape

Question 9

Elimination

Answer 9

immune surveillance, the tumor is eliminated

Question 10

Equilibrium

Answer 10

tumor dormancy, a balance between death and survival of tumor cells

Question 11

Escape

Answer 11

growing tumor, cells have developed immunoevasive mutations

Question 12

CTLs

Answer 12

recognize and kill infected/tumor cells via TCR activation and 3 signals are needed for activation.

Question 13

Signal 1

Answer 13

TCR binds peptide presented by APC on MHC class I

Question 14

Signal 2

Answer 14

costimulatory signal transmitted by CD28-B7 interaction between T cell and
APC
* APCs get help from T cells to upregulate stimulation molecules

Question 15

Signal 3

Answer 15

providedbycytokines(IL-2,IL-12),inducingproliferationanddifferentiation into CTL

Question 16

The cancer immunity cycle

Answer 16

DCs acquire tumor antigen, migrate to the lymph node, and activate a de novo T cell response

Question 17

Immune selection

Answer 17

Development of low immunogenic clones
* Low immunogenic clones can not be detected by the immune system and thus have a selective advantage

Question 18

Immune subversion

Answer 18

The tumor cells alter the immune response to their own benefit (from tumor protective to tumor promoting response)

Question 19

Cancer immunotherapy

Answer 19

Immunotherapy is treatment that uses a person’s own immune system to fight cancer. Immunotherapy can boost or change how the immune system works so it can find and attack cancer cells.

Question 20

Types of cancer immunotherapy

Answer 20

Monoclonal antibodies targeting cancer cells
* Reversing immune checkpoint blockade * anti-CTLA-4antibodies
* anti- PD-1/anti PDL-1 antibodies
* Enhancement of APC activity/therapeutic vaccines * Adoptive transfer of effector cells (eg CAR T-cells)

Question 21

CAR

Answer 21

Chimeric antigen receptor

Question 22

Cancer antigen

Answer 22

A protein or other molecule that is found only on cancer cells and not on normal cells

Question 23

Do all cancers express antigens?

Answer 23

This is an important caveat, because cancer cells are poor antigen-presenting cells, and the immune system, therefore, depends on cross-presentation by dendritic cells (DCs) to detect the presence of TSAs.

Question 24

CAR-T cells

Answer 24

CAR T cell therapy is a type of cancer immunotherapy treatment that uses immune cells called T cells that are genetically altered in a lab to enable them in locating in destroying cancer cells more effectively.

Question 25

How can CAR-T cells treat cancer?

Answer 25

T cells are white blood cells that find and fight illness and infection throughout the body. Each T cell has a receptor that can recognize antigens (proteins or molecules that are recognizable by the immune system). When the immune system recognizes foreign or abnormal antigens, it can work to destroy them. But cancer cells sometimes have antigens that body doesn't recognize as abnormal. As a result, the immune system may not send T cells to fight cancer cells. In other cases, the T cells may not be able to clear the cancer cells. Chimeric antigen receptor T cells are cells that are genetically engineered (changed) in a laboratory. They have a new receptor so they can bind to cancer cells and kill them. Different types of cancer have different antigens. Each kind of CAR T cell therapy is made to fight a specific kind of cancer antigen. So a CAR T cell therapy made for one type of cancer won't work against another type of cancer.

Question 26

Immune checkpoint blockade?

Answer 26

A type of drug that blocks proteins called checkpoints that are made by some types of immune system cells, such as T cells, and some cancer cells. These checkpoints help keep immune responses from being too strong and sometimes can keep T cells from killing cancer cells.