tumour immunology

Question 1

aetiology of cancer

Answer 1

Transformation of germline cells: inheritable cancers (<10%, Rb, BRCA1, 2)

Transformation of somatic cells: noninheritable cancers (>90%)

Environmental factors:
UV (skin cancer), chemicals (lung cancer), pathogens (HPV causes cervical cancer, helicobacter causes stomach cancer)

Question 2

name the 6 hallmarks of cancer. the functional capabilities that allow cancer to survive and proliferate

Answer 2

• resisting cell death
• sustaining proliferative signalling
• evading growth supressors
• activating invasion and metastasis
• enabling replicative immortality
• inducing angiogenesis

Question 3

define the new emerging hallmarks of cancer and 2 enabling characteristics.

Answer 3

hallmarks:
- deregulating cellular energetics
- avoiding immune destruction

enabling characteristics:
- genome instability and mutation
- tumour presenting inflammation

Question 4

define cancer immunosurveilance theory.

Answer 4

idea that the Immune system can recognize and destroy nascent transformed cells, normal control

Question 5

define cancer immunoediting.

Answer 5

Immunoediting is the dynamic process by which the immune system suppresses tumor growth (elimination), maintains dormant tumor cells (equilibrium), and unintentionally promotes immune-resistant variants that enable tumor progression (escape).

Question 6

is the immune system capable of cancer recognition?

Answer 6

Immune system is capable of early recognition and elimination of cancer cells in the process of malignant transformation

Mediated by various components of the immune system (T-cells, NKT cells, NK cells)
Scarce evidence for its existence in humans

Question 7

define and contrast tumour specific antigens and tumpour associated antigens.

Answer 7

Tumour Specific Antigens (TSA)
Are only found on tumours
As a result of point mutations or gene rearrangement
Derive from viral antigens
- this is something which can be targetted in vaccines and therapies or whatevrr

Tumour Associated Antigens (TAA)
Found on both normal and tumour cells, but are overexpressed on cancer cells
Developmental antigens which become derepressed. (CEA)
Differentiation antigens are tissue specific
Altered modification of a protein could be an antigen
eg in pancreatic cancer, a protein released by the pancreas is increased, so used to detect

Question 8

Q: What are the two main categories of tumor antigens?

Answer 8

A: Tumor antigens are classified into tumor-associated antigens (TAAs) and tumor-specific antigens (TSAs) based on the expression pattern of their parental genes.

Question 9

Q: What are tumor-associated antigens (TAAs)?

Answer 9

A: TAAs are self-proteins expressed in cancer cells that result from malignant transformation, leading to overexpression of normal proteins, tissue-specific antigens, or cancer-testis antigens.

Question 10

Q: What are the three types of consequences observed in TAAs?

Answer 10

A:
(1) Overexpression of normal proteins (gene overexpressed),
(2) Expression of tissue-specific differentiation antigens, and
(3) Expression of proteins restricted to the testes (cancer germline/cancer testis antigens).

Question 11

Q: What are tumor-specific antigens (TSAs)?

Answer 11

A: TSAs are proteins expressed exclusively by tumor cells and arise from mutations (neoantigens), oncoviral antigens from viruses, or expression of tumor-specific endogenous retroviruses (TSERVs).

Question 12

Q: What are the origins of tumor-specific antigens (TSAs)?

Answer 12

A: TSAs originate from mutations (neoantigens), viral oncogenic transformation (oncoviral antigens), or tumor-specific endogenous retroviruses (TSERVs).

Question 13

define tumour escpae

Answer 13

Immune responses change tumours such that tumours will no longer be seen by the immune system

Question 14

define evasion

Answer 14

Tumours change the immune responses by promoting immune suppressor cells

Question 15

the immune system has a dual response in cancer, what are these responces

Answer 15

• immunosurveillance
• immunoediting of tumour

Question 16

name the active immunotherapy / vaccines available for cancer

Answer 16

• killed tumour vaccine
• purified tumour antigens
• professional APC-based vaccines
• cytokine - and costimulator-enhanced vaccines
• dna vaccines
• viral vectors

Question 17

name the passive immunotherapy for cancer

Answer 17

• adoptive cellular therapy (T cells)
• anti-tumour antibodies

Question 18

how are cell-based therapies used?

Answer 18

• can activate a patients immune system to attack cancer
• can be used as delivery vehicle to target theraputic genes to attack tumour
• dont always act directly on tumour but can travel to other areas to stimulate immune cells

Question 19

dendritic cell vaccines

Answer 19

• take blood from patient
• isolate wbc
• create dendritic cells in the lab
• activate these to have cytotoxic properties by adding drug ect
• inject these back into patient

Question 20

T-cell therapy

Answer 20

• take tumour biopsy
• isolate the cells from the tumour biopsy
• grow these in the lab
• they will amplify and grow
• make them melanoma reactive
• can then put them back into patients using transfusion

Question 21

what other cells can be used during cell therapy

Answer 21

• natural killer cells
• stem cells
• tumour cells

Question 22

trojan horse

Question 22

trojan horse

Answer 22

• take blood from patient
• squirt blood ontp plastic and macrophages are made without having to do anything
• chuck virus at macrophage, allowing the macrophages to carry it to the tumour
• virus kills tumour

Question 23

what is tumour hypoxia and why is it problematic?

Answer 23

• when the tumour is big enough, the vasculature doesn’t serve the middle of the tumour
• this creates hypoxic tumour cells
• this is an issue because we cant adminiter radiotherapy because ocygen free radicals are needed
• and because of the poor supply of blood vessels, chemotherapy cant get there
• the outside of the tumour will die but the inside will survive and repopulate
• supresses immune system
• increased tumour hypoxia after therapy

Question 24

outline some mechanisms of how cancer cells evade the immune system.

Answer 24

- tumour cells stop expressing their TAA or their MHC-I which presents the antigen - tumours start to express immune checkpoint ligans which bind to T cells, inhibiting its activation - cytokine release to supress T cells, dendritic cells and macrophages - tumour recruit tregs which release immunosuppressive cytokines - continuous antigen exposure leads to T-cell exhaustion - tumour cells suppround themselves with dense layer of glycocalx making them undetectable

Question 25

outline and brielfy explain the different types of immunotherapy

Answer 25

Immune Checkpoint Inhibitors: Drugs that block immune checkpoints (e.g., PD-1/PD-L1 or CTLA-4) to "release the brakes" on T cells and enhance their activity against tumors. CAR-T Cell Therapy: Genetically engineered T cells are programmed to target specific cancer cells. Cancer Vaccines: Stimulate the immune system to attack specific tumor antigens. Cytokine Therapy: Uses immune-stimulating molecules (e.g., interleukins or interferons) to boost immune cell activity. Monoclonal Antibodies: Lab-engineered antibodies target cancer-specific antigens to kill cancer cells or enhance immune recognition. Immune Modulators: General activators of the immune system, such as Bacillus Calmette-Guérin (BCG) for bladder cancer.

Question 26

outline why immunotherapy cannot be used generically for all cancer types.

Answer 26

Low Tumor Immunogenicity: cells can mutate to stop expressing antigens or some cancers express very few antigens anyway Immunosuppressive Microenvironment: Tumors secrete cytokines or form barriers such as dense stromal tissue that block immune cell infiltration. "Cold Tumors": Lack T-cell infiltration, making them unresponsive. Resistance: Tumors adapt to evade immune attack by lacking the pathways targetted by drugs Toxicity: Risk of autoimmune or inflammatory side effects. eg CAR-T may lead to cytokine release syndrome which is life-threatening Cancer-Specific Challenges: Solid tumours are harder to target than blood cancers.