Academic Sinica MIB group Introduction to 4th part 1. how to categorize the patient's pathology profile into immune phenotype in order to predict the prognosis of immunotherapy

1. Elements of cancer immunity and the cancer-immune set point
Correlates of the response to immunotherapy
Daniel S. Chen & Ira Mellman
Academia Sinica, MIB Chen group
Nature , volume 541 , published:19 January 2017
Speaker :
Ting-Wei Lin
National Taiwan University, Genome and System Biology
Lab Journal Reading
4th part

2. Zou, W., Wolchok, J. D., & Chen, L. (2016). PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations. Science Translational
Medicine, 8(328), 328rv4.
10-40%
anti-PD-L1/PD-1 antibodies
Variation of the clinical response to the immunotherapy
anti-CTLA4, IL-2
(even less response rate)

3. Predictive correlates of response with PD-L1 IHC staining
IHC(Immunohistochemistry)
Herbst, R. S., Soria, J.-C., Kowanetz, M., Fine, G. D., Hamid, O., Gordon, M. S., … Hodi, F. S. (2014). Predictive correlates of response to the anti-
PD-L1 antibody MPDL3280A in cancer patients. Nature, 515(7528), 563–7.
IC(Immune Cells)
TC(Tumor Cell)

4. How these IHC score produce?

6. Tumeh, P. C., Harview, C. L., Yearley, J. H., Shintaku, I. P., Taylor, E. J. M., Robert, L., … Ribas, A. (2014).
PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature, 515(7528), 568–71.
Requires Pre-existing CD8+ T cell mediated immune response
Prembrolizumab
Quantitative immunohistochemistry
Multiplex quantitative immunofluorescence T cell receptor sequencing

7. non-small cell lung cancer metastatic urothelial carcinoma
Stratified the patient survival
with the level of cytokine and TC/IC score
TC:tumor cell with PD-L1 expression, IC:infiltrating immune cell
Fehrenbacher, L., (2016). The Lancet, 387(10030), 1837–1846. Rosenberg, J. E.,…(2016). The Lancet, 387(10031),

8. Three basic immune profiles correlating with responseCancer
Inflamed tumour
Immune-excluded tumour
Immune-desert tumour
1. CD4/CD8 + T cell in Tumor Parenchyma
2. High expression of PD-L1 on TC or IC
3. Pro-inflammatory and effector cytokine
TC: Tumor cell, IC: Infiltrating immune cell
1. IC not penetrating the parenchyma
2. still abundant immune cells around tumor
1. few or no CD8+ T cell
2. Poor response

9. Inflamed tumour
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2
3
4
5
6

10. Immune-excluded tumour
Joyce, J. A., & Fearon, D. T. (2015). T cell exclusion, immune privilege, and the tumor
microenvironment. Cancer Immunology and Immunotherapy, 348(6230).
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2
3

11. Immune-desert tumour
Zou, W., Wolchok, J. D., & Chen, L. (2016). PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and
combinations. Science Translational Medicine, 8(328), 328rv4.
1
2
3

12. The tumor immunity spectrum and cycle
Convert to inflamed phenotype with combinationsRespond favorably to checkpoint inhibition
Hegde, P. S., Karanikas, V., & Evers, S. (2016). The where, the when, and the how of immune monitoring for cancer immunotherapies in the era of checkpoint inhibition. Clinical Cancer Research, 22(8)

13. Predicting response with Personalized cancer immunotherapy paradigm
Kim, J. M., & Chen, D. S. (2016). Immune escape to PD-L1/PD-1 blockade: Seven steps to success (or failure). Annals of Oncology, 27(8)

14. Thank you!Thank you!