Radiotherapy can be used in combination with immunotherapy to help the body's immune system fight cancer. Radiation damages cancer cells, causing them to release proteins that allow white blood cells to target the cancer cells. Low doses of radiation activate receptors on cancer cells to release more proteins without suppressing the immune response. The combination approach utilizes irradiated cancer cells to increase the effectiveness of immunotherapy against primary and secondary cancers. However, very high radiation doses cause cancer cells to enter a wound healing state where they secrete chemicals that inhibit the immune attack.

1. Building Cancer
Immunity with
Radiotherapy
Gorby Castillo 5380253

2. What is Cancer?
• A disease involving abnormal cell growth that can spread to
other parts of the body

4. Causes/Symptoms
• Causes
• 90% Environmental (carcinogens from tobacco/food, radiation,
infection, lifestyle)
• 10% Genetic/hereditary
• Symptoms
• Dependent on cancer type

5. Treatments
• Surgery
• Radiotherapy
• Chemotherapy
• Immunotherapy

6. Surgery
• Direct tumor removal

7. Chemotherapy
• Anti-cancer drugs

8. Radiotherapy
• Damage DNA of cancer cells using ionizing radiation

9. Immunotherapy
• Use the body’s immune system to fight cancer cells

10. Radiotherapy: Mechanism
• DNA/Membrane Damage

11. Cell Death from Radiation
• Mitotic catastrophe
• Apoptosis
• Necrosis
• Autophagy
• Senescence

12. Mitotic Catastrophe
• Premature mitosis

13. Apoptosis
• Programmed cell death

14. Necrosis
• Loss of cell membrane integrity/DNA degradation

15. Autophagy
• Excessive catabolism of components, eating itself

16. Senescence
• Permanent cell cycle arrest

17. Closer look: Radiotherapy
• Can damage normal cells
• Different cancer types have different radiosensitivity
• High (leukemia, lymphoma, ovarian/testicular), ~30 Gy
• Moderate (breast, prostate, lung, colon), ~70 Gy
• Low (skin, kidney), too high to be safe
• Curability is usually reverse of radiosensitivity
• Therefore usually requires chemotherapy
• Intensity vs exposure constraint

18. Advances in Radiotherapy
• Advanced image guiding systems – higher precision
• SABR (stereotactic ablative body radiation)
• Synchrotron MRT (microbeam radiotherapy)
• Pre-clinical testing due to unknown reason for low local tissue
sensitivity

19. SABR
• Daily, minute, precise doses of radiation (2 Gy)

20. Synchrotron MRT
• High flux X-rays segmented into a lattice of micro-planar
beams separated by plains of low dose radiation, allowing very
high doses (over 100 Gy) of radiation

21. Immunotherapy: Mechanism
• White blood cells will attack targeted cancer cells

22. Closer Look: Immunotherapy
• Mechanism: body’s immune system will fight cancer cells
• Three “E”’s of immunoediting
• Elimination
• Equilibrium
• Escape
• Limited to cancer cells which release high immunoactivators
• Cancer cells which release little/no immunoactivators are not
affected

23. Elimination
• Cancer cells release immunoactivators which act as receptors
for white blood cells to target

24. Equilibrium
• Surviving cancer cells grow and multiply/improve their
resistance to white blood cells

25. Escape
• New cancer cell variants continue to attack the body without
resistance from immune system

26. Combining Radiotherapy and
Immunotherapy
• Positive Effects (2-15 Gy)
• Irradiated cancer cells are a good source of diverse
immunoactivators
• Radiation activates MHC class I receptors in cancer cells, releasing
more immunoactivators
• New immunoactivators are memorized and used for secondary
cancers
• Negative Effects (Over 15 Gy)
• Cancer cells enters “wound healing” state when dosage is too
high, releasing immunosupressant chemicals
• Immunosupressant chemicals prevent/inhibit release of
immunoactivators such has MHC class I receptors

27. Radiotherapy +
Immunotherapy

28. Conclusion
• Radiotherapy has become more precise due to technological
advancement
• Immunotherapy is limited to cancer cells which release
enough immunoactivators
• Radiotherapy can allow utilization of irradiated cancer cells in
immunotherapy to increase effectiveness, with low radiation
doses more effective in this case

29. References
• http://www.sciencedirect.com/science/article/pii/S03043835
15000300
• http://www.annualreviews.org/doi/abs/10.1146/annurev.imm
unol.22.012703.104803
• http://www.cancernetwork.com/cancer-management
• http://www.who.int/mediacentre/factsheets/fs297/en/