Tumor immunology describes the interaction between cancer cells and the immune system. While intrinsic and environmental factors can cause dysregulated cell growth leading to cancer, the immune system provides innate and adaptive responses to identify and eliminate tumor cells. However, cancer cells can evade the immune system through various mechanisms. Cancer immunotherapy seeks to boost the immune response against cancer through cytokines, monoclonal antibodies, and vaccines to help treat certain cancers.

1. Tumor Immunology
By: Noor Al.Marhoon.

2. Content
• Cancer
• Immune surveillance
• Immune evasion
• Cancer immunotherapy

3. Introduction
• Cell growth & cell death are normally balanced
so that a stable number of cells are maintained
in a given tissue. Occasionally, however, cells
arise that no longer respond to the usual checks
and balances for division and death. These are
tumor cells.

4. Cancer
• How does cancer arise?
Dysregulated cell growth & proliferation
=> Transformation
A clone of cells expanding indefinitely
=> A tumor
Tumor cells => the body and cause diseases
=> Cancer

5. What causes dysregulated cell growth
& proliferation?
• Intrinsic factors - Genetic mutations on
Oncogenes & Tumor suppressor genes
• Environmental factors – Radiation, Carcinogens
• Microbial infections – Viruses (viral oncogenes)
Bacteria

6. Key Concepts in Tumor immunity
1. Tumors express Ags that are recognized as foreign
by the host immune system.
2. Immune responses frequently fail to prevent the
growth of tumors.
3. The immune system can be activated by external
stimuli to effectively kill tumor cells and eradicate
tumors.

7. Tumor Antigens
1. Tumor-Specific Transplantation Antigens
(TSTAs):
Antigen that are expressed on tumor cells but
not on normal cells were called tumor-specific.

8. Tumor Antigens
2. Tumor-Associated Transplantation Antigens
(TATAs):
Tumor antigens that are also expressed on
normal cells were called tumor-associated
antigens; in most cases, these antigens are
normal cellular constituents whose expression
is aberrant or dysregulated in tumors.

9. Immune Surveillance
A. Innate:
1. NK cells:
NK cells kill many types of tumor cells, especially
cells that have reduces class I MHC expression
and can escape killing CTLs.

11. Immune Surveillance
A. Innate:
2. Cytokines:
Cytokines with antitumor activity are secreted by
macrophages.
- TNF: TNF-α and TNF-β can stimulate necrosis of
the tumor cell . TNF-α also inhibit angiogenesis,
the growth of new blood vessels by decreasing
blood flow to the tumor.

12. Immune Surveillance
- Interferons:
• Are another group of cytokines with anti tumor
activity.
• IFN-α , IFN-β and IFN-γ have all been shown to
increase MHC I expression on tumor cell surface.
• IFN-γ may also inhibit proliferation of tumor cells.

13. Immune Surveillance
B. Adaptive:
- antibodies: are known to be generated against
certain tumor-specific antigens present on the
surface of malignant cell.
- CTL: direct killing!
- DTH: activating macrophages, which attack and
kill tumor cell.

14. Immune Evasion
A. Antibody enhancement of tumor growth:
The antitumor antibodies may bind to the
antigens on the tumor cells, masking the
antigens and blocking the ability of CTL cells to
bind and kill the tumor cell. Antibody bound to
tumor antigen may inhibit binding of Fc
receptors on macrophages, dendritic cells, and
NK cells.

15. Immune Evasion
B. Antibody modulation of tumor antigen:
The antigens disappear for a time and then
reappear when the antibody is eliminated. Cells
that do not express the antigen are no longer
target of other adaptive immune responses.
C. Modulation of MHC I expression:
Class I MHC expression may be down-regulated
on tumor cells so that they cannot be recognized
by CTLs.

16. Cancer Immunotherapy
A. Cytokine therapy.
B. Monoclonal
Antibodies.
A. Cancer vaccines.

17. Cancer Immunotherapy
B. Monoclonal antibodies:

18. Summary
• Cancer cells have unregulated rates of cell
growth and invade healthy tissue.
• Genetic mutations, radiation, Viruses and
Bacteria are the causes of dysregulated cell
growth & proliferation.
• Innate immune responses against tumors
include NK cell killing of tumor and macrophage
production of antitumor cytokines.
• Adaptive immune response against tumors
include generation of antitumor Abs, CTL, and
DTH reactions.

19. Summary
• Immune evasion by tumor cells facilitate
survival of malignant cells.
• Cancer immunotherapy is designed to increase
the immune response against cancer cells,
Cytokines and monoclonal antibodies have
proven to have some limited effects in treating
certain cancers. Vaccination, either to prevent
development of a type of cancer or to inhibit
recurrence of a tumor within a patient,
continues to be explored.

20. Reference
• Lippincott’s illustrated reviews ,
Immunology; Thao Doan MD, Roger Melvold
PhD , Susan Viselli PhD, Carl Waltenbaugh
PhD .