1. CD8+ T Cells Contribute to Lung Cancer Progression in a PD-1 Dependent Fashion Stephanie Chang, Saeed Arefanian, Ryuji Higashikubo, Daniel Kreisel, Andrew Gelman, Alexander S. Krupnick Division of Cardiothoracic Surgery

2. CD8+ Memory Cells Current strategies for immunotherapy focus on activation and transfer of CD8+ cytotoxic T lymphocytes

3. Data from our lab

4. Higher Sarcoma in CD8-/- mice B6B6 CD8-/- 3-Methylcholantherene injection in flank B6B6 CD8-/-

5. Lower Lung Cancer Incidence in CD8-/- mice Urethane induction B6B6 CD8-/-

6. B6B6 CD8-/- 10 6 B16 melanoma expressing ovalbumin

7. B6B6 CD8-/- 10 6 Lewis Lung Carcinoma, B16 melanoma, expressing ovalbumin

8. unlike the case for most malignancies CD8 + T cells contribute to tolerance induction and more rapid growth of lung cancer this process is specific to lung cancer tumor cells themselves and not necessarily the lung environment since CD8 + T cell accelerated growth of lung cancer occurs even after injection of cell lines into the flank

9. Immunologic Phenotype

10. Tolerogenic role of PD-1/PD-L1 PD-1 blocking Ab (RMP1-14) ovalbumin expressing LLC cell line ns

11. Immunoregulation of lung cancer is unique among solid tumors Just because an immunotherapy works in another cancer does not mean it will work in lung cancer Unlike melanoma, lung cancer has a simple “co- stimulatory phenotype” of MHC Class I and PD-L1 Reversal of “CD8+ T suppressor cells” may explain the overwhelming success of PD-1/PDL-1 blockade in lung cancer The nature/identity of “CD8+ suppressor T cells” is still being explored in our laboratoryConclusion

12. Acknowledgements Thoracic Immunology Lab Alexander S. Krupnick, MD Daniel Kreisel, MD, PhD Andrew E. Gelman, PhD Stephanie Chang, MD Ryuji Higashikubo, PhD WenJun Li, MD Kelsey Toth Jihong Zhu Reza Ghasemi, PhD Jim Hsiao, PhD

13. 

14. B6B6 CD8-/- 10 6 Lewis Lung Carcinoma, B16 melanoma, EG7 Lymphoma expressing ovalbumin