Building Cancer Immunity with RadiotherapyGorby Castillo 5380253

What is Cancer?• A disease involving abnormal cell growth that can spread to

other parts of the body

Causes/Symptoms• Causes• 90% Environmental (carcinogens from tobacco/food, radiation,

infection, lifestyle)• 10% Genetic/hereditary

• Symptoms• Dependent on cancer type

Treatments• Surgery• Radiotherapy• Chemotherapy• Immunotherapy

Surgery• Direct tumor removal

Chemotherapy• Anti-cancer drugs

Radiotherapy• Damage DNA of cancer cells using ionizing radiation

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

Radiotherapy: Mechanism• DNA/Membrane Damage

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

Mitotic Catastrophe• Premature mitosis

Apoptosis• Programmed cell death

Necrosis• Loss of cell membrane integrity/DNA degradation

Autophagy• Excessive catabolism of components, eating itself

Senescence• Permanent cell cycle arrest

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

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

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

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

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

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

Elimination• Cancer cells release immunoactivators which act as receptors

for white blood cells to target

Equilibrium• Surviving cancer cells grow and multiply/improve their

resistance to white blood cells

Escape• New cancer cell variants continue to attack the body without

resistance from immune system

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

Radiotherapy + Immunotherapy

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

References• http://

www.sciencedirect.com/science/article/pii/S0304383515000300

• http://www.annualreviews.org/doi/abs/10.1146/annurev.immunol.22.012703.104803

• http://www.cancernetwork.com/cancer-management• http://www.who.int/mediacentre/factsheets/fs297/en/