Cancer Immunology- basics

1. D r T H A N G A M . V
I M V S C
CANCER IMMUNOLOGY

2. CANCER OR NEOPLASIA
 A new growth of abnormal tissue that is often
uncontrolled and progressive.

3. CANCER CELLS
 Immune system views cancer cells as
“Self altered cells that have excaped normal growth
regulating mechanism”
Production of new cells in our body is regulated so as to
maintain the number of any particular cell
When certain cells no longer respond to normal growth-control
mechanisms it leads to neoplasm or cancer

4. CLASSIFICATION OF TUMORS

5. HISTORY OF CANCER IMMUNOLOGY
 Paul Ehrlich conceived the
idea that tumor cells can be
recognized as foreign and
eliminated by the immune
system

6. HISTORY OF CANCER IMMUNOLOGY
 In 1957 Burnet and
Thomas coined the term
immune surveillance
which implies that the
normal function of the
immune system is to scan
the body for emerging
malignant cells and
destroy them

7. IMMUNE SYSTEM IS BOTH A
CANCER PROMOTER AND
SUPPRESSOR

8. How does immune cells identify tumor or cancer
cells?
 Cancer cells express tumour-associated antigens
(TAAs) or tumour-specific antigens (TSAs) that can
be recognised by the immune system as foreign
elements.
 Decreased expression of MHC’s
 Lipid assymetry of cancer cells
Phosphatidylethanolamine (PE), a lipid membrane
component which exists only in the inner leaflet of cell
membrane under normal circumstances, has increased
surface representation on the outer membrane in cancer
cells

9. INNATE IMMUNITY
Alterations in the cancer cells (changes in the composition of their cell
surface proteins)
expression of tumor-associated antigens
recognized by complement proteins
complement-mediated death

10.  Activation of complement proteins has been reported in
local and/or systemic biological fluids of cancer patients
AND
 cancer tissues from patients diagnosed with
neuroblastoma, lung cancer, ovarian cancer, and a variety
of others

11. Expression of MHC class I becomes altered or reduced in cancer cells
activation of NK cells via activating receptors present on NK cell surface
Nk cell surface receptors bind to surface glycoproteins present on the
tumors
programmed cell death occurs
by tumor-necrosis factor-alpha- (TNF-α-) dependent release of
cytoplasmic granules
perforin and granzymes form pores in cell membranes

12. NEUTROPHILS PROMOTE CANCER
SYNTHESIS
 Proteases such as neutrophil elastase present in
neutrophil granules facilitate growth of cancer cells
 Other proteases in the neutrophil granules assist in
cleaving extracellular matrix proteins, thus allowing cancer
invasion and metastasis

13. ADAPTIVE IMMUNITY
Formation of neoantigens, due to tumorigenesis/oncogenesis
phagocytosed by antigen-presenting cells (APCs) or pinocytosed by dendritic cells
for antigen processing
MHC class II molecules present exogenous peptides of tumor antigens,
MHC class I molecules present endogenous peptides derived from cancer
antigens on the APC
to the antigen-specific T cell receptor on CD4+ T cells or CD8+ T cells

14. Activation of CD4+ T cells by MHC class II on APC
primes them for subsequent exposures to that particular antigenic
peptide/MHC class II complex, thus forming memory T cells
IL-2 is also produced when T cells are activated and further promotes T cell
proliferation
cytolytic T cell-mediated lysis of cancer cells

15. CANCER IMMUNOEDITING

16. How cancers solve the challenge of host
immunity

17. Cancers can overwhelm the host immune system
 Malignancies outrace the host immune system
 No sufficient time for manipulation of the host
immune response to achieve meaningful therapeutic benefits
CANCER IMMUNE
SYSTEM

18. Cancers can hide from the immune system
By losing target antigen expression
By reducing antigen presentation by diminshed expression of MHC class I or class
II on malignant cells or APC’s
through disordered angiogenesis and dense collagenous stroma

19. CANCERS CAN SUBVERT THE IMMUNE SYSTEM
 Malignant cells can secrete cytokines to create an immune suppressive
microenvironment
 Anticytokine antibodies can target these immunosuppressive networks

20. CANCER CAN DEFEND AGAINST T CELL ASSAULTS
 Immune checkpoints are used by cancers to
deactivate T cells

21. CANCER CELLS CAN ERECT SHIELD TO DEFLECT
IMMUNE SYSTEM
 T cells that cannot infiltrate into tumors cannot exert
significant antitumor effects
 Cancer may shed antigens into the tumor
microenvironment thereby diverting T- cells

22.  Presence of soluble and membrane-bound complement regulatory proteins
(CRPs) inhibit various steps in the multiple complement signaling pathways
protecting cancer cells against complement-mediated injury
 PD-1 and PD-L1 are types of proteins found on cells in body.
 PD-1 protein is found on immune cells called T cells. It normally acts as a type
of "off switch" that helps in keeping the T cells from attacking other cells in the
body.
 PD-1 attaches to PD-L1, a protein found on some normal (and cancer) cells.
This interaction basically tells the T cell to leave the other cell alone and not
attack it. Some cancer cells have large amounts of PD-L1, which helps them
hide from immune attack.

24. IMMUNOTHERAPY
 Stimulation of the immune system to treat cancer,
improving on the system's natural ability to fight cancer

26. NON SPECIFIC IMMUNE STIMULATION
 Drugs are given that increase the overall immune response of
the body
 For example a patient suffering from bladder cancer after
removal of the cancerous part in the bladder lining is given BCG
 Bacillus Calmette-Guerin (BCG) is the main intravesical
immunotherapy for treating early-stage bladder cancer.
 The body’s immune system cells are attracted to the bladder and
activated by BCG, which in turn affects the bladder cancer cells.

27. T – CELL TRANSFER THERAPY
 A sample of T cells is taken from the blood through a process
called apheresis.
 First a tube is put into a vein in each arm. One tube removes the
blood and passes it into an apheresis machine.
 The machine takes out only T cells and the rest of blood cells and
normal blood fluid go back into your body through the tube in
other arm.
 In the lab, they change the T cells by genetically engineering the T
cell.

28.  The T cell is now a CAR T-cell. CAR stands for chimeric antigen
receptor. These CAR T-cells are designed to recognise and target
a specific protein on the cancer cells.
 These changed T cells are grown and multiplied in the lab.
 Once there are enough cells grown a drip containing these cells
are put back into bloodstream
 The aim is for the CAR T-cells to then recognise and attack the
cancer cells.

29. IMMUNE CHECKPOINT INHIBITORS
 checkpoints – molecules on certain immune cells that need
to be activated (or inactivated) to start an immune
response.
 PD-1 or PD-L1
 CTLA-4

30. DRUGS THAT TARGET PD-1 OR PD-L1
 PD-1 is a checkpoint protein on T cells which normally acts as a
type of “off switch” that helps in keeping the T cells from
attacking other cells in the body.
 It does this when it attaches to PD-L1, a protein on some normal
(and cancer) cells. When PD-1 binds to PD-L1 present in cancer
cells , it basically tells the T cell to leave the other cell alone.
 Some cancer cells have large amounts of PD-L1, which helps
them evade immune attack.
 Monoclonal antibodies that target either PD-1 or PD-L1 can
block this binding and boost the immune response against
cancer cells.

31. Drugs that target CTLA-4
 CTLA-4 is another protein on some T cells that acts
as a type of “off switch” to keep the immune system
in check.
 Monoclonal antibodies that target CTLA-4 will be
helpful in treating cancers

32. MONOCLONAL ANTIBODIES
 Monoclonal antibodies (mAb or moAb) are antibodies that are all
clones of a unique parent cell.
 Monoclonal antibodies can have monovalent affinity, in that they
bind to the same epitope
 Monoclonal antibodies attach to specific proteins on cancer cells. This
flags the cells so the immune system can find and destroy those cells.

33. CANCER VACCINES
 Antigen vaccines
These vaccines are made from special proteins
(antigens) in cancer cells. Scientists have worked out
the genetic codes of many cancer cell proteins
 Whole cell vaccines
A whole cell vaccine uses the whole cancer cell, not
just a specific cell protein (antigen), to make the
vaccine

34.  Dendritic cell vaccines
Dendritic cells help the immune system recognise
and attack abnormal cells, such as cancer cells.
 DNA vaccines
These vaccines are made with DNA from cancer
cells.