1. immunotherapy in
brain tumors
Farshid Arbabi Clinical Oncologist

2. Immune Subsystems
 The human immune system can be classified into two
different subsystems
 Innate immunity (or non-specific immune system), which
reacts rapidly to any foreign substance
 Adaptive immunity (or specific immune system), which
provides a somewhat slower reaction to specific foreign
substances

3. Innate Immunity
 The innate immune system includes inherited physical and
biochemical structures present from birth that protect the
body from invading substances Innate immune defenses are
non-specific
 Respond to pathogens in a generic way
 This system does not confer long-lasting immunity against
a pathogen1
 The innate immune system is the dominant system of host
defense in most organisms

4. Innate Immunity
 Innate immunity includes two layers of protection
 External (primary) defenses
 Internal (secondary) defenses

5. Complement System
 The complement system
 A group of 20+ proteins
 Stimulates other immune system elements
 Can also cause lysis of bacteria and certain other cells
 Interferons and proteins are the two main types of non-specific
antimicrobial proteins

6. Adaptive Immunity
 Also called specific or acquired immunity
 Develops upon exposure to a pathogen or foreign substance
 Creates immunological memory
 Substances causing this response are antigens
 The immune response can destroy anything containing the
antigen, whether bacteria or cancer cells
 Adaptive immunity is highly specific to its molecular
structural characteristics
 This leads to an enhanced immune response to subsequent
encounters with that same pathogen
1. Abbas et al, 2011

8. Lymphocytes
 Lymphocytes are involved in adaptive immunity
 There are various classes of lymphocytes
 B lymphocytes recognize soluble antigens and develop into antibody-
secreting cells
 Helper T lymphocytes recognize antigens on the surfaces of antigen-
presenting cells(APCs) and secrete cytokines
 Cytokines stimulate different mechanisms of immunity and
inflammation

9. Lymphocytes
 Cytotoxic T lymphocytes recognize antigens on infected cells and kill
these cells
 Regulatory T cells suppress and prevent immune response (e.g., to self
antigens)
 NK cells use receptors with more limited diversity than T or B cell
antigen receptors

10. Types of Specific Immune Response
Humoral Immunity
 Mediated by proteins, including
antibodies, in the blood and other
bodily fluids
 Produces a cascade of chemicals
from the complement system
 Antibodies are produced by plasma
cells (derived from B cells)
 Bind to specific antigens,
inactivating them and/or marking
them for destruction
Cellular Immunity
 Also called cell-mediated immunity
 Mediated by T cells
 May attack target cells directly or
indirectly by activating other immune
cells
 Enhances the inflammatory response
 Cellular immunity primarily targets
antigenic molecules and
microorganisms

11. T-cell Activation and Tumor
Suppression
 Antigen-presenting cells (APCs) take up foreign antigens, are
processed by the APC and then bound to major
histocompatibility complex (MHC) molecules on the APC
surface
 MHC molecules present the processed antigen to T cells
 T cells interact with the complex formed by antigen bound
to MHC molecule, producing a
T-cell activation signal known as signal 1
1. Bowes et al, 2014

12. T-cell Activation and Tumor
Suppression
 Complete activation requires a second APC signal, known as
signal 2
 Once activated, T cells can directly kill tumor cells that
express the antigen for which it has specificity
 Activated T cells can release cytokines that kill tumor cells or
chemicals that attract other immune cells (e.g.,
macrophages), to destroy tumor cells
1. Bowes et al, 2014

14. Fas/ Fas ligand

17. Immune system hampering
• Body
• Diminished T Cell responsiveness
• Increase regulatory T Cells
• Decrease IgG production
• Tumor microenvironment
• diminished MHC
• Increase Regulatory T Cells
• inhibitory cytokines
• PD-L1
• Fas Ligand
• Myloid derived cells
• CTLA4

18. What is immunotherapy?
 The NCI defines immunotherapy as “treatment to boost or
restore the ability of the immune system to fight cancer,
infections, and other diseases”
 Tumor immunotherapy Aims to augment the weak host
immune response (active immunity)
 Or to administer tumor-specific antibodies or T cells, a form of
passive immunity
1. National Cancer Institute, 2014; 2. Abbas et al, 2011

19. IMMUNOTHERAPY METHODS
 Non specific
 cytokines
 interferon
 interlukines
 Drugs
 Thalidomide
 Lenalidomide

20. Check point inhibitors
CTLA4 regulation
 inhibition
 Ipilimumab
PD-1, PD-L1
 Nivolumab
 pembrolizumab

21.  Nivolumab
 pembrolizumab

22. Vaccines
 dendritic cells
 antigens + danger signal

23. Adoptive Cell Therapy

24. Mono clonal antibody
 Herceptin