Exam 4 Lecture 22: Cancer

Question 1

What is the difference between a benign tumor and a malignant tumor?

Answer 1

Benign: tissue that grows abnormally but encapsulated, limited in size, non invasive
Malignant: grows abnormally and spreads to other tissues

Question 2

What are some essential characteristics of cancer cells?

Answer 2

Stimulate own growth, ignore growth inhibiting factors, avoid apoptosis, develop blood supply, invade the tissues (metastasis), constant replication to expand, evade immune response

Question 3

How do macrophages recognize and kill cancer cells?

Answer 3

Recognize “eat me” (calreticulin) and “don’t eat me” (CD47) signals
Kill by engulfment

Question 4

How do NK cells recognize and kill cancer cells?

Answer 4

Recognize cell stress with inhibitory and activating receptors of MHC I
Requires signals from 2+ receptors

Question 5

How do CD8+ T cells recognize and kill cancer cells?

Answer 5

Recognize: antigen recognizes target cell, T cell becomes polarized
Kill by kiss of death- release performing and granzyme to kill target cell

Question 6

What are TILs and what antigens do they recognize?

Answer 6

Tumor infiltrating lymphocytes
Recognize:
Tumor associated antigens
Self proteins that are usually expressed by some normal cells, now expressed by tumor cells

Tumor specific antigens (aka neoantigens)
Expressed only by tumor cells, unique proteins resulted from mutations, novel peptides with new epitopes for recognition by T cells

Question 7

What are the 3 stages of cancer immunoediting?

Answer 7

Elimination: immune cells kill most cancer cells
Equilibrium: cancer growth and death is equal
Escape: cancer cells escape immune control through immune suppression and antigen changes

Question 8

What are 3 ways that tumor can escape the immune system?

Answer 8

1. Antigen modulation: changing antigen expression
2. Tumor induced immune suppression: release of immunoregulatory factors & expression of ligands for inhibitory signal
3. Recruitment of immunosuppressive cells: Tregs, MDSC, TAMs

Question 9

4 types of immunotherapies

Answer 9

1. Antibody targeted therapies
2. Adoptive T cell transfer
3. Checkpoint blockade Dendritic
4. Dendritic cell based therapies

Question 10

How do antibodies target and kill cancer cells?

Answer 10

Naked antibodies:
Direct tumor cell killing
Immune mediated tumor cell killing
Vascular and stoma cell ablation

Antibody-drug complexes:
Target radioactivity or drugs to cancer cells

Question 11

What is adoptive T cell therapy? What are CAR T cells?

Answer 11

Genetic engineering of T cells

Chimeric antigen receptor T cells: recognition of antigens not restricted to MHC molecules but requires expression of antigen in surface of tumor cells
Consist of heavy and light chain of antibody plus intracellular T cell signaling

Question 12

What is checkpoint blockade therapy?

Answer 12

Blocking an inhibitory signal on T cells to rescue T cell exhaustion and promote killing of cancer cells