Lecture Notes - Tumor Immunology - week 1

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)