colorectal cancer

1. Project Supervisor: Dr. Sahar Fazal
* Rimsha Farooq (bbs153009)
Syeda Rehab
Gillani(bbs153012)
CUST Islamabad 31
March 2018

2. CUST Islamabad 31
March 2018
Colorectal Cancer Immunity
and Inflammation
Topic of
Presentation

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Colorecta
l Cancer
A malignancy that arises from
the inner lining of the colon
cancer.
Risk factor of colon
cancer include the family
history or ulcerative
colitis.

4. CUST Islamabad 31 March 2018
• Complex and multi-
faceted role in cancer
• Interaction and signaling
Immune
Cells
Tumor
Progression
Tumor
Suppression
Introduction

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Anti Tumor
Immune
Responses

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Anti Tumor
Immune
Responses

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31 March 2018
Immuno-
Surveillance
Immune cells patrol the
body monitoring for the
altered cells that become
cancer in a process known
as “Immunosurveillance”.
NK
cells
Macr
opha
ges
DCs
Neutr
o-
phils
CD8+
T
cells
CD4
+ Th
1
CD4
+Th
17

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2018
Immuno-editing
and Immune
Deficiencies In Cancer
• “Three Es of cancer
immunoediting”.Elimination
Escape
Equilibrium

9. Pro-tumor Immune
Responses
• Microenvironment
• Release of TGF
β
First
mechanism
• Recruitment of
immunosuppressive
cells i.e. Tregs and
CD11b+Gr1+
myeloid-derived
suppressor cells
Second
mechanism
CUST Islamabad
31 March 2018

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Conditioning The
Tumor Micro-
environment
• Tumor-associated
Macrophages
• Angiogenesis promotion and
homing of
cancer cells by (HMGB1)
• Proliferation of CCs
Homing
Inflammation
Proliferation
Metastasis

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Chronic
Inflammation
and Cancer
Microenvironment
initiated
Damage to ROS
Pro survival pathways
The most notable is the
gram-negative bacillus
Helicobacter pylori which is
associated with gastric
cancer and has been shown
both in murine models and
humans to cause chronic
inflammation that promotes
cancer.

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Immune Cells
As Prognostic
Factors
• Presence of specific
immune cells as prognostic
factor
• Growth and survival of
tumor cells, angiogenesis
• Specific immune responses
within the tumor site were
found to influence clinical
outcome at all stages of
CRC.
Immune cells in
cancer prognosis
Memory T
cells Th1
CD8+ T
cells
CTLs
Cytotoxic
types
NK cells
Antigen
presenting
cells DCs

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Immunotherapy
• Harnesses the immune
system
• Anti-tumor immune
response through strategies
such as vaccination in
combination with immune
stimulatory cytokines

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Different
Immunotherapeuti

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Cancer Vaccines
• Tumor-associated antigens
• Surveillance to protect against
its regrowth.

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Whole Tumor Vaccine
• Autologous whole tumors have
been used as cancer vaccines to
induced cytotoxic anti-tumor
immune responses
• immune response generated by
whole tumor vaccines is
generally insufficient to
provide benefit to patients

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Peptide Vaccines
• Develop an immune response
against a specific known tumor
antigen
• Peptides employed are
designed for MHC Class I, the
MHC recognized by CD8+
cytotoxic T cells

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Viral Vector Vaccine
• The body has already
developed multiple pathways
to recognize.

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DC Vaccines
The central cells for this process
are DCs, which can provide all
three signals for a productive
anti-tumor immune response and
thus, many groups have
attempted to utilize DCs for
vaccination

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Adoptive Cell
Transfer (ACT) Therapy
Extracts autologous T cells from
the tumors of patients, activates
them with cytokines and expands
them into large numbers in vitro,
all in preparation for transfer
back into the patient

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2018
Antibody-based Cance
Immunotherapy
• The pathway of inhibiting
VEGF as a treatment for
Colorectal cancer using mAbs.
• mAbs targeting the inhibitory
immune receptors CTLA-4,
programmed cell death 1 (PD-
1), and PD-1 ligand (PD-L1)
have produced successful
results in patients with
advanced melanoma and
NSCLC

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Combined Immuno-
therapy:
Key To Success?
Stimulating an immune response
via vaccines, in combination with
blocking inhibitory pathways
such as CTLA-4 or PD-1

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Conclusions
Tremendous progress has been
made in understanding the role
of the immune system in driving
the development of Colorectal
Cancer.

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