Module 2: Tumor Immunology (Week 1)
LECTURE 1: BASIC TUMOR IMMUNOLOGY Monday 1/10/2018
1. Lymphoid-Myeloid differentiation patterns
Cellular elements of blood arise from pluripotent HSC in the bone marrow. HSC produces 2 types of progenitor
cells: lymphoid progenitor & myeloid progenitor. B cells (differentiate in bone marrow) & T cells (differentiate in
thymus) have antigen receptors; other cells do not. Unlike B/T cells, ILC (innate lymphoid cells) & NK cells lack
antigen specificity.
Differentiated B cells plasma cell, T cell effector T cell (T helpers, T cytotoxic, T regulatory).
Immature dendritic cells (DC): enter tissue and act as phagocytic cells, matures after contact with antigen; DC can
be derived from myeloid/lymphoid progenitors. Monocytes: entering tissues differentiate into macrophages
Mature DC DO NOT PHAGOCYTISE
2. Defense systems against pathogens
Epithelium: most important barrier against pathogens, if disrupted require help from immune system
Chemical & enzymatic elements (complement C3, defensins, etc) + innate immune cells (macrophage,
granulocyte, NK) provide rapid cell-mediated response when epithelium is breached
, Module 2: Tumor Immunology (Week 1)
Adaptive immune response slower process, able to induce memory to provide faster & more efficient
response on 2nd exposure to the same antigen
3. Adaptive response (antibody-mediated)
Lag phase: body produces antibodies pathogens are being neutralized by cellular response.
Primary response: immunoglobulin level increases in serum (decreases when infection is overcome).
Secondary response: quicker & higher effectivity on 2nd encounter (memory cells involvement don’t need
much activation).
4. Antigen-presenting cells (APC) – key players in immune system
2 professional APC: dendritic cells & macrophages taking up antigens to break them down (into oligopeptides)
& present them to MHC class I/II. DC: watchdogs of the body, always patrolling for abnormal cells, Macrophages:
scavengers
DC maturation: precursors in bone marrow (marker: CD34+) exposed to cytokines (GM-CSF, IL-4)
immature DC (in resting/non-infected tissue, can only take up antigen, marker: CD1a+) exposure to antigen OR
presence of other cytokines (TNF alpha, CD40, LPS, GM-CSF, IL-4) mature DC (able to take up antigen & present
antigen to MHC, marker: CD83+)
, Module 2: Tumor Immunology (Week 1)
Tumor antigen processing by APC:
Tumor starts growing, some dies d/t necrosis release tumor
antigens tumor antigens recognized by DC taken up by DC
& into lymph nodes exposure of DC & tumor antigen to naïve T
cells T cell maturation (bound to DC) activation &
proliferation of T cells T cells migrate to tumor site
eradication by apoptosis
5. Mellman cancer immunity cycle
Destruction of tumor cells by chemotherapy,
radiation, or targeted therapy releasing
TAA/TSA TAA/TSA taken up by APC (uptake
can be enhanced by vaccine, IFN alfa, GM-CSF,
CD40 agonist, or TLR agonist) antigen
presentation priming & activation of naïve T
cells (enhanced by anti-CTLA4, IL-2, IL-12, etc)
activated T cell migrates into tumor
microenvironment infiltrate TME recognize
cancer cells (enhanced by CAR) killing of tumor
cells (enhanced by anti-PD1/PD-L1, IDO inhibitor)
, Module 2: Tumor Immunology (Week 1)
6. DC activity
DC receptors:
a. Fc receptor: binds to antigen-antibody
complex internalization
b. Toll-like receptors (TLR): binds viral &
bacterial antigens, can also bind to certain
ligands
Type I/II TLR: bacteria
Type III TLR: viral dsDNA (specific)
Type IV TLR: endotoxin/LPS
Type IX TLR: CpG hypomethylation
(virus/bacteria)
c. CD36 receptor: binds apoptotic bodies
d. CD91 receptor: binds heat shock proteins
Immature DC is activated via its TLR when presented to microbes receptor ligands can also bind to TLR to
mimic actual bacterial infection (i.e. vaccination strategy)
LECTURE 1: BASIC TUMOR IMMUNOLOGY Monday 1/10/2018
1. Lymphoid-Myeloid differentiation patterns
Cellular elements of blood arise from pluripotent HSC in the bone marrow. HSC produces 2 types of progenitor
cells: lymphoid progenitor & myeloid progenitor. B cells (differentiate in bone marrow) & T cells (differentiate in
thymus) have antigen receptors; other cells do not. Unlike B/T cells, ILC (innate lymphoid cells) & NK cells lack
antigen specificity.
Differentiated B cells plasma cell, T cell effector T cell (T helpers, T cytotoxic, T regulatory).
Immature dendritic cells (DC): enter tissue and act as phagocytic cells, matures after contact with antigen; DC can
be derived from myeloid/lymphoid progenitors. Monocytes: entering tissues differentiate into macrophages
Mature DC DO NOT PHAGOCYTISE
2. Defense systems against pathogens
Epithelium: most important barrier against pathogens, if disrupted require help from immune system
Chemical & enzymatic elements (complement C3, defensins, etc) + innate immune cells (macrophage,
granulocyte, NK) provide rapid cell-mediated response when epithelium is breached
, Module 2: Tumor Immunology (Week 1)
Adaptive immune response slower process, able to induce memory to provide faster & more efficient
response on 2nd exposure to the same antigen
3. Adaptive response (antibody-mediated)
Lag phase: body produces antibodies pathogens are being neutralized by cellular response.
Primary response: immunoglobulin level increases in serum (decreases when infection is overcome).
Secondary response: quicker & higher effectivity on 2nd encounter (memory cells involvement don’t need
much activation).
4. Antigen-presenting cells (APC) – key players in immune system
2 professional APC: dendritic cells & macrophages taking up antigens to break them down (into oligopeptides)
& present them to MHC class I/II. DC: watchdogs of the body, always patrolling for abnormal cells, Macrophages:
scavengers
DC maturation: precursors in bone marrow (marker: CD34+) exposed to cytokines (GM-CSF, IL-4)
immature DC (in resting/non-infected tissue, can only take up antigen, marker: CD1a+) exposure to antigen OR
presence of other cytokines (TNF alpha, CD40, LPS, GM-CSF, IL-4) mature DC (able to take up antigen & present
antigen to MHC, marker: CD83+)
, Module 2: Tumor Immunology (Week 1)
Tumor antigen processing by APC:
Tumor starts growing, some dies d/t necrosis release tumor
antigens tumor antigens recognized by DC taken up by DC
& into lymph nodes exposure of DC & tumor antigen to naïve T
cells T cell maturation (bound to DC) activation &
proliferation of T cells T cells migrate to tumor site
eradication by apoptosis
5. Mellman cancer immunity cycle
Destruction of tumor cells by chemotherapy,
radiation, or targeted therapy releasing
TAA/TSA TAA/TSA taken up by APC (uptake
can be enhanced by vaccine, IFN alfa, GM-CSF,
CD40 agonist, or TLR agonist) antigen
presentation priming & activation of naïve T
cells (enhanced by anti-CTLA4, IL-2, IL-12, etc)
activated T cell migrates into tumor
microenvironment infiltrate TME recognize
cancer cells (enhanced by CAR) killing of tumor
cells (enhanced by anti-PD1/PD-L1, IDO inhibitor)
, Module 2: Tumor Immunology (Week 1)
6. DC activity
DC receptors:
a. Fc receptor: binds to antigen-antibody
complex internalization
b. Toll-like receptors (TLR): binds viral &
bacterial antigens, can also bind to certain
ligands
Type I/II TLR: bacteria
Type III TLR: viral dsDNA (specific)
Type IV TLR: endotoxin/LPS
Type IX TLR: CpG hypomethylation
(virus/bacteria)
c. CD36 receptor: binds apoptotic bodies
d. CD91 receptor: binds heat shock proteins
Immature DC is activated via its TLR when presented to microbes receptor ligands can also bind to TLR to
mimic actual bacterial infection (i.e. vaccination strategy)
