Patho neoplasm 11/05

Question 1

Cancer cells must develop adaptations to avoid ………..

Answer 1

detection by the innate and adaptive immune response.

Question 2

What is one important common adaptation characteristic for cancer cells to avoid detection?

Answer 2

overexpression of programmed cell death ligand 1 (PD-L1) on the tumor cell surface.

Question 3

Where is programmed cell death ligand 1 (PD-L1)?

Answer 3

On tumor cells

Question 4

Where is programmed cell death protein (PD-1)?

Answer 4

on immune cells - natural killer (NK) cells, T cells, and B cells.

Question 5

PD-L1 binds PD-1. What effect?

Answer 5

Downregulates immune cell (natural killer (NK) cells, T cells, and B cells) activity.

Question 6

When PD-L1 binds to PD-1 on an activated T-cell, it converts it to ……………

Answer 6

exhausted T-cell

Question 7

Exhausted T-cells primarily express …………….

Answer 7

Immunoinhibitory molecules.

Question 8

Effect of exhausted T-cells? (2)

Answer 8

Exhausted T-cells primarily express immunoinhibitory molecules and are unable to effectively destroy cancer cells with perforins/granzymes (Choice E) or to secrete immunostimulatory cytokines (eg, IL 2

Question 9

What cannot secrete exhausted T-cells?

Answer 9

Immunostimulatory cytokines

Question 10

exhausted T-cells are unable …..

Answer 10

unable to effectively destroy cancer cells with perforins/granzymes

Question 11

How to counter the overexpression of PD-L1?

Answer 11

In order to counter the overexpression of PD-L1 by certain tumors, patients can receive immunotherapy medications that block PD-1 (eg, pembrolizumab) or PD-L1 (eg, atezolizumab), which restores anti-tumor T-cell activity.

Question 12

What medications block PD-1?

Answer 12

pembrolizumab

Question 13

What medications block PD-L1?

Answer 13

atezolizumab

Question 14

What is the effect of immunotherapy which targets PD-L1 or PD-1?

Answer 14

restored anti-tumor T cell activity.

Question 15

What 4 mechanisms of tumor cells to avoid immune system? (apart PD-L1)

Answer 15

Down-regulation of I MHC;
Induction of T-cell energy;
Increased secretion of immunoinhibitory cytokines;
Selection of tumor cells with minimal immunogenicity.

Question 16

Adaptations cancer cells. Down-regulation of class I MHC. Effect?

Answer 16

Limits neoantigen expression on the tumor cell surface.

Question 17

Adaptations cancer cells. Induction of T-cell energy (ie dormant state). Effect?

Answer 17

Tumor cells eliminate costimulatory surface molecules (CD80/86) required for T-cell activation; this induces T-cell anergy (ie, a dormant state).

Question 18

Adaptations cancer cells. Increased secretion of immunoinhibitory cytokines. Effect?

Answer 18

Tumors increase production of cytokines (eg, IL-10, tumor growth factor beta) that dampen the immune response.

Question 19

Adaptations cancer cells. Selection of tumor cells with minimal immunogenicity. Effect?

Answer 19

Cells most visible to the immune system are quickly destroyed; this generates a selective pressure on the tumor cell population that promotes proliferation of the least immunologically visible cancer cells.

Question 20

Limits neoantigen expression on the tumor cell surface. By what mechanism?

Answer 20

Down-regulation of class I MHC.

Question 21

Tumor cells eliminate costimulatory surface molecules (CD80/86) required for T-cell activation. It leads to what?

Answer 21

Induction of T-cell energy (ie dormant state).

Question 22

Tumors increase production of cytokines (eg, IL-10, tumor growth factor beta) that dampen the immune response. It is generally described as what avoidance mechanism?

Answer 22

Increased secretion of immunoinhibitory cytokines

Question 23

Cells most visible to the immune system are quickly destroyed; this generates a selective pressure on the tumor cell population that promotes proliferation of the least immunologically visible cancer cells. How it is generally named as avoidance mechanism?

Answer 23

Selection of tumor cells with minimal immunogenicity

Question 24

Tumor cells often increase (not decrease) expression of …………and…………. species

Answer 24

ROS and nitrogen species

Question 25

Tumor cells often increase (not decrease) the expression of reactive oxygen and nitrogen species. What effect?

Answer 25

It exerts a negative effect on T-cell function in the tumor microenvironment.

Question 26

PD-L1 - PD-1 binding reduces the ………… cell population.

Answer 26

PD-L1–PD-1 binding reduces the effector T-cell population.

Question 27

Dendritic cell activation is primarily mediated by CD40-ligand (CD40-L), a surface molecule present on ………………

Answer 27

Activated T-helper cells