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Elements of cancer immunity and the cancer-immune set point

W
Weiting Lin

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

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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
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)
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), 5637. IC(Immune Cells) TC(Tumor Cell)
How these IHC score produce?
Elements of cancer immunity and the cancer-immune set point
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), 56871. Requires Pre-existing CD8+ T cell mediated immune response Prembrolizumab Quantitative immunohistochemistry Multiplex quantitative immuno鍖uorescence T cell receptor sequencing
non-small cell lung cancer metastatic urothelial carcinoma Strati鍖ed the patient survival with the level of cytokine and TC/IC score TC:tumor cell with PD-L1 expression, IC:in鍖ltrating immune cell Fehrenbacher, L., (2016). The Lancet, 387(10030), 18371846. Rosenberg, J. E.,(2016). The Lancet, 387(10031),
Three basic immune pro鍖les correlating with responseCancer In鍖amed 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-in鍖ammatory and effector cytokine TC: Tumor cell, IC: In鍖ltrating 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
In鍖amed tumour 1 2 3 4 5 6
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). 1 2 3
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
The tumor immunity spectrum and cycle Convert to in鍖amed 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)
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)
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Elements of cancer immunity and the cancer-immune set point

  • 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), 5637. 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), 56871. Requires Pre-existing CD8+ T cell mediated immune response Prembrolizumab Quantitative immunohistochemistry Multiplex quantitative immuno鍖uorescence T cell receptor sequencing
  • 7. non-small cell lung cancer metastatic urothelial carcinoma Strati鍖ed the patient survival with the level of cytokine and TC/IC score TC:tumor cell with PD-L1 expression, IC:in鍖ltrating immune cell Fehrenbacher, L., (2016). The Lancet, 387(10030), 18371846. Rosenberg, J. E.,(2016). The Lancet, 387(10031),
  • 8. Three basic immune pro鍖les correlating with responseCancer In鍖amed 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-in鍖ammatory and effector cytokine TC: Tumor cell, IC: In鍖ltrating 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
  • 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). 1 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 in鍖amed 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)