SINGLE CELL OMICS IN IMMUNOTHERAPY
INTRODUCTION TO THE COURSE
-Only Cancer Stem Cells have to capacity for self-renewal and tumorigenesis (formation of tumor) and these cells
make up less than 1% of the tumor. Understanding these cells has an enormous therapeutic potential.
-A minority of tissue-specific stem cell populations are responsible for tissue development, regeneration and
repair.
-The immune system’s dynamic cellular heterogeneity is essential for fighting off the variety of attacking
pathogens.
Immunotherapy = A type of treatment in which the immunesystem is modulated (enhanced or suppressed) with
the ultimate goal of curing/alleviating a disease.
Single-cell (multi)omics = the profiling of single cells sampled from heterogenous populations of cells from
different cellular states, where the normal development and disease processing can be studied and dissected at a
single cell resolution. (1)
1. Jehan Z. Single-cell omics: An overview. In: Single-Cell Omics: Volume 1: Technological Advances and
Applications [Internet]. Elsevier; 2019 [cited 2020 Sep 5]. p. 3–19. Available from:
https://linkinghub.elsevier.com/retrieve/pii/B9780128149195000014
https://books.google.nl/books?id=3vabDwAAQBAJ&lpg=PP1&hl=nl&pg=PA6#v=onepage&q&f=false
Online resources:
- http://flowbook.denovosoftware.com/
- https://www.microscopyu.com/
- https://www.nature.com/articles/s12276-018-0071-8 (Article)
THE CANCER-IMMUNITY CYCLE
,NK cells
If a cell has mutated they will downregulate MHC
expression to prevent T-cell recognition, but this will
active the NK cells to kill the cell.
B no MHC expression and low expression of activating
ligands.
C low expression of MHC but high expression of
activating ligands.
T-cells
Natural T-regs are suppressive and derive directly from the thymus progenitor cell.
Naïve T cells can become induced T-regs, Th1, Th2 and Th17 cells, dependent on cytokines in surroundings.
Th1 cells – autoimmune disease and anti-tumor immunity
Th2 cells – Parasite infection allergy
Th17 cells – Autoimmune disease and microbial immunity
Type 1 PAMPs on DCs promote Th1 maturation, Type 2 PAMPs promote Th2 maturation.
To inhibit auto-immune
responses Tregs can
prevent the activation of
DCs. Tregs bind to CTLA4
and CD80/86 on DCs and
rip off their molecules so
the Mature DC can no
longer co-stimulate a CD4
T-cell which will not get
activated.
Tregs will also inhibit tumor
immunity by directly killing
mature DCs with
granzymes and so prevent
priming of tumor-specific
cytotoxic T cells (CTLs).
MHC class 1 = endogenous
antigens
MHC class 2 = exogenous
antigens
, Cross presentation
Exogenous antigens can be taken into the endocytic route and be presented on MHC class 1 molecules.
This is important because remnants of dying tumour cells will be exogenous.
THE CANCER IMMUNITY CYCLE (FORREAL)
The ‘E’ Hypothesis
When tumor cells exist the first fase is Elimination, in which the immunecells try to kill all the tumor cells. In most
cases this doesn’t work and it leads to an
Equilibrium in which the tumors mutate to
be less recognised by the immunecells.
This eventually leads to the escape of the
tumor of the immunesystem. This is the
point where patients usually come into the
clinic.
INTRODUCTION TO THE COURSE
-Only Cancer Stem Cells have to capacity for self-renewal and tumorigenesis (formation of tumor) and these cells
make up less than 1% of the tumor. Understanding these cells has an enormous therapeutic potential.
-A minority of tissue-specific stem cell populations are responsible for tissue development, regeneration and
repair.
-The immune system’s dynamic cellular heterogeneity is essential for fighting off the variety of attacking
pathogens.
Immunotherapy = A type of treatment in which the immunesystem is modulated (enhanced or suppressed) with
the ultimate goal of curing/alleviating a disease.
Single-cell (multi)omics = the profiling of single cells sampled from heterogenous populations of cells from
different cellular states, where the normal development and disease processing can be studied and dissected at a
single cell resolution. (1)
1. Jehan Z. Single-cell omics: An overview. In: Single-Cell Omics: Volume 1: Technological Advances and
Applications [Internet]. Elsevier; 2019 [cited 2020 Sep 5]. p. 3–19. Available from:
https://linkinghub.elsevier.com/retrieve/pii/B9780128149195000014
https://books.google.nl/books?id=3vabDwAAQBAJ&lpg=PP1&hl=nl&pg=PA6#v=onepage&q&f=false
Online resources:
- http://flowbook.denovosoftware.com/
- https://www.microscopyu.com/
- https://www.nature.com/articles/s12276-018-0071-8 (Article)
THE CANCER-IMMUNITY CYCLE
,NK cells
If a cell has mutated they will downregulate MHC
expression to prevent T-cell recognition, but this will
active the NK cells to kill the cell.
B no MHC expression and low expression of activating
ligands.
C low expression of MHC but high expression of
activating ligands.
T-cells
Natural T-regs are suppressive and derive directly from the thymus progenitor cell.
Naïve T cells can become induced T-regs, Th1, Th2 and Th17 cells, dependent on cytokines in surroundings.
Th1 cells – autoimmune disease and anti-tumor immunity
Th2 cells – Parasite infection allergy
Th17 cells – Autoimmune disease and microbial immunity
Type 1 PAMPs on DCs promote Th1 maturation, Type 2 PAMPs promote Th2 maturation.
To inhibit auto-immune
responses Tregs can
prevent the activation of
DCs. Tregs bind to CTLA4
and CD80/86 on DCs and
rip off their molecules so
the Mature DC can no
longer co-stimulate a CD4
T-cell which will not get
activated.
Tregs will also inhibit tumor
immunity by directly killing
mature DCs with
granzymes and so prevent
priming of tumor-specific
cytotoxic T cells (CTLs).
MHC class 1 = endogenous
antigens
MHC class 2 = exogenous
antigens
, Cross presentation
Exogenous antigens can be taken into the endocytic route and be presented on MHC class 1 molecules.
This is important because remnants of dying tumour cells will be exogenous.
THE CANCER IMMUNITY CYCLE (FORREAL)
The ‘E’ Hypothesis
When tumor cells exist the first fase is Elimination, in which the immunecells try to kill all the tumor cells. In most
cases this doesn’t work and it leads to an
Equilibrium in which the tumors mutate to
be less recognised by the immunecells.
This eventually leads to the escape of the
tumor of the immunesystem. This is the
point where patients usually come into the
clinic.
