Professor Cebon discusses the link between the immune system and cancer, immunotherapy and the current research being undertaken to develop new treatments that target cancer cells. This session was jointly hosted by BreaCan and Olivia Newton-John Cancer and Wellness Centre.

1. Your Immunity System & Cancer
Jonathan Cebon
Austin Health, Olivia Newton-John Cancer Research Institute
&
Olivia Newton John Cancer & Wellness Centre

3. Cancer immunosurveillance theory
1967
Tumours can be recognized and
eliminated by the immune system.
Macfarlane Burnet (1899–1985).

4. Melanoma in donor renal graft - 16 years
after initial resection
Melanoma in donor renal graft - 16 years
after initial resection
MacKie NEJM. 2003

5. Case 1
Mrs R
• Past: Crohn’s disease
– In remission
1998
• Primary melanoma diagnosed
– Abdominal wall, high risk, stage IIC
June 99
• 1st recurrence: skin nodules
July 99
• 2nd recurrence: Brain tumour
– Treated with radiotherapy

6. August 1999
Admission to hospital with Crohn’s disease flare
– Spontaneous regression of
– Multiple subcutaneous metastases
– 3cm liver metastasis
Case 1
June 1999 Feb 2000

7. Case 1
May 2001
• 3rd melanoma recurrence: R proximal humerus
– Resection + prosthesis
May-Jun 2001
– Vitiligo gradually developed over face, trunk, arms
Dec 2001
Gall bladder surgery
pigmented masses
No live melanoma
Melanin-laden immune
cells (macrophages)

8. Case 1
• Last clinical review Jun 2014
– Alive & well
– No evidence of melanoma

9. Tumor infiltrating lymphocytes: association with improved survival
Melanoma

10. Summary
• Stage 4 melanoma: metastatic disease in brain, liver,
bone, skin, mucosal surfaces
• Median survival 7 months
• Spontaneous remission associated with
autoimmunity Crohn’s colitis
• Discussion point: can autoimmunity be harnessed as
a therapeutic tool?

11. Immune Checkpoint Blockade
Ribas NEJM June 2012

12. T-cell receptor: Antigen-MHC
CD28: B7
CTLA-4: B7

13. Feb 2014 June 2014
Melanoma in Liver
Response to Yervoy

14. Immune Checkpoint Blockade
Ribas NEJM June 2012

15. LUDWIG CANCER RESEARCH
September 2013 April 2014
Anti-PD-1 Malignant Melanoma
Pulmonary metastases
70y M

16. Combination anti-CTLA4 & anti-PD-1
Wolchok et al June 2013

17. Slide 18
Presented By Jedd Wolchok at 2013 ASCO Annual Meeting

18. Cancer Risk following Renal Transplant
ANZ Dialysis & Transplant register 1997 8618 patients
Cancer Number Risk Ratio
CNS Lymphoma 17 >1000
Ureter 10 250
Parathyroid 2 200
Kaposi Sarcoma 18 86
Vulva/Vagina 40 43
Penis 7 24
Cervix 65 17
Bladder 54 7
Kidney 8 7
NH Lymphoma 83 7
Liver 8 6
Colon 50 2
Breast 42 1

19. PD-1 inhibitors
Active in multiple cancer types (response rates reported at June 2015)
• Melanoma (17-40%)
• Lung (10-30%)
• Kidney (12-29%)
• Bladder (25%)
• Ovarian (6-23%)
• Head & Neck (14-20%)
• Hodgkins Lymphoma (87%)
• Gastric
• Triple-ve breast
• Mesothelioma
• HCC
• Cancers with mismatch repair gene defects

20. Summary & Conclusions
• Cancer responds to immune attack
• Understanding the underlying science has
enabled effective new therapies to be
developed
• Clinical trials are underway to evaluate
these treatments in many different cancer
types