Patho neoplasm 11/05 Flashcards
Cancer cells must develop adaptations to avoid ………..
detection by the innate and adaptive immune response.
What is one important common adaptation characteristic for cancer cells to avoid detection?
overexpression of programmed cell death ligand 1 (PD-L1) on the tumor cell surface.
Where is programmed cell death ligand 1 (PD-L1)?
On tumor cells
Where is programmed cell death protein (PD-1)?
on immune cells - natural killer (NK) cells, T cells, and B cells.
PD-L1 binds PD-1. What effect?
Downregulates immune cell (natural killer (NK) cells, T cells, and B cells) activity.
When PD-L1 binds to PD-1 on an activated T-cell, it converts it to ……………
exhausted T-cell
Exhausted T-cells primarily express …………….
Immunoinhibitory molecules.
Effect of exhausted T-cells? (2)
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
What cannot secrete exhausted T-cells?
Immunostimulatory cytokines
exhausted T-cells are unable …..
unable to effectively destroy cancer cells with perforins/granzymes
How to counter the overexpression of PD-L1?
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.
What medications block PD-1?
pembrolizumab
What medications block PD-L1?
atezolizumab
What is the effect of immunotherapy which targets PD-L1 or PD-1?
restored anti-tumor T cell activity.
What 4 mechanisms of tumor cells to avoid immune system? (apart PD-L1)
Down-regulation of I MHC;
Induction of T-cell energy;
Increased secretion of immunoinhibitory cytokines;
Selection of tumor cells with minimal immunogenicity.
Adaptations cancer cells. Down-regulation of class I MHC. Effect?
Limits neoantigen expression on the tumor cell surface.
Adaptations cancer cells. Induction of T-cell energy (ie dormant state). Effect?
Tumor cells eliminate costimulatory surface molecules (CD80/86) required for T-cell activation; this induces T-cell anergy (ie, a dormant state).
Adaptations cancer cells. Increased secretion of immunoinhibitory cytokines. Effect?
Tumors increase production of cytokines (eg, IL-10, tumor growth factor beta) that dampen the immune response.
Adaptations cancer cells. Selection of tumor cells with minimal immunogenicity. Effect?
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.
Limits neoantigen expression on the tumor cell surface. By what mechanism?
Down-regulation of class I MHC.
Tumor cells eliminate costimulatory surface molecules (CD80/86) required for T-cell activation. It leads to what?
Induction of T-cell energy (ie dormant state).
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?
Increased secretion of immunoinhibitory cytokines
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?
Selection of tumor cells with minimal immunogenicity
Tumor cells often increase (not decrease) expression of …………and…………. species
ROS and nitrogen species
Tumor cells often increase (not decrease) the expression of reactive oxygen and nitrogen species. What effect?
It exerts a negative effect on T-cell function in the tumor microenvironment.
PD-L1 - PD-1 binding reduces the ………… cell population.
PD-L1–PD-1 binding reduces the effector T-cell population.
Dendritic cell activation is primarily mediated by CD40-ligand (CD40-L), a surface molecule present on ………………
Activated T-helper cells
