CD8+ T Cells Contribute to Lung Cancer Progression in a PD-1 Dependent Fashion Stephanie Chang,...
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Transcript of CD8+ T Cells Contribute to Lung Cancer Progression in a PD-1 Dependent Fashion Stephanie Chang,...
![Page 1: CD8+ T Cells Contribute to Lung Cancer Progression in a PD-1 Dependent Fashion Stephanie Chang, Saeed Arefanian, Ryuji Higashikubo, Daniel Kreisel, Andrew.](https://reader035.fdocuments.in/reader035/viewer/2022062803/56649f1e5503460f94c35972/html5/thumbnails/1.jpg)
CD8+ T Cells Contribute to CD8+ T Cells Contribute to Lung Cancer Progression in a Lung Cancer Progression in a
PD-1 Dependent FashionPD-1 Dependent Fashion
Stephanie Chang, Saeed Arefanian, Ryuji Higashikubo, Daniel Kreisel, Andrew Gelman, Alexander S. Krupnick
Division of Cardiothoracic Surgery
![Page 2: CD8+ T Cells Contribute to Lung Cancer Progression in a PD-1 Dependent Fashion Stephanie Chang, Saeed Arefanian, Ryuji Higashikubo, Daniel Kreisel, Andrew.](https://reader035.fdocuments.in/reader035/viewer/2022062803/56649f1e5503460f94c35972/html5/thumbnails/2.jpg)
CD8+ Memory Cells CD8+ Memory Cells Current strategies for immunotherapy focus on activation and transfer ofCD8+ cytotoxic T lymphocytes
![Page 3: CD8+ T Cells Contribute to Lung Cancer Progression in a PD-1 Dependent Fashion Stephanie Chang, Saeed Arefanian, Ryuji Higashikubo, Daniel Kreisel, Andrew.](https://reader035.fdocuments.in/reader035/viewer/2022062803/56649f1e5503460f94c35972/html5/thumbnails/3.jpg)
Data from our labData from our lab
![Page 4: CD8+ T Cells Contribute to Lung Cancer Progression in a PD-1 Dependent Fashion Stephanie Chang, Saeed Arefanian, Ryuji Higashikubo, Daniel Kreisel, Andrew.](https://reader035.fdocuments.in/reader035/viewer/2022062803/56649f1e5503460f94c35972/html5/thumbnails/4.jpg)
Higher Sarcoma in CD8-/- Higher Sarcoma in CD8-/-
micemiceB6 B6 CD8-/-
3-Methylcholantherene injection in flank
B6 B6 CD8-/-
![Page 5: CD8+ T Cells Contribute to Lung Cancer Progression in a PD-1 Dependent Fashion Stephanie Chang, Saeed Arefanian, Ryuji Higashikubo, Daniel Kreisel, Andrew.](https://reader035.fdocuments.in/reader035/viewer/2022062803/56649f1e5503460f94c35972/html5/thumbnails/5.jpg)
Lower Lung Cancer Incidence in CD8-/- Lower Lung Cancer Incidence in CD8-/-
micemiceUrethane induction
B6 B6 CD8-/-
![Page 6: CD8+ T Cells Contribute to Lung Cancer Progression in a PD-1 Dependent Fashion Stephanie Chang, Saeed Arefanian, Ryuji Higashikubo, Daniel Kreisel, Andrew.](https://reader035.fdocuments.in/reader035/viewer/2022062803/56649f1e5503460f94c35972/html5/thumbnails/6.jpg)
B6 B6 CD8-/-
106 B16 melanoma expressing ovalbumin
![Page 7: CD8+ T Cells Contribute to Lung Cancer Progression in a PD-1 Dependent Fashion Stephanie Chang, Saeed Arefanian, Ryuji Higashikubo, Daniel Kreisel, Andrew.](https://reader035.fdocuments.in/reader035/viewer/2022062803/56649f1e5503460f94c35972/html5/thumbnails/7.jpg)
B6 B6 CD8-/-
106 Lewis Lung Carcinoma, B16 melanoma, expressing ovalbumin
![Page 8: CD8+ T Cells Contribute to Lung Cancer Progression in a PD-1 Dependent Fashion Stephanie Chang, Saeed Arefanian, Ryuji Higashikubo, Daniel Kreisel, Andrew.](https://reader035.fdocuments.in/reader035/viewer/2022062803/56649f1e5503460f94c35972/html5/thumbnails/8.jpg)
• 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
![Page 9: CD8+ T Cells Contribute to Lung Cancer Progression in a PD-1 Dependent Fashion Stephanie Chang, Saeed Arefanian, Ryuji Higashikubo, Daniel Kreisel, Andrew.](https://reader035.fdocuments.in/reader035/viewer/2022062803/56649f1e5503460f94c35972/html5/thumbnails/9.jpg)
Immunologic Immunologic PhenotypePhenotype
![Page 10: CD8+ T Cells Contribute to Lung Cancer Progression in a PD-1 Dependent Fashion Stephanie Chang, Saeed Arefanian, Ryuji Higashikubo, Daniel Kreisel, Andrew.](https://reader035.fdocuments.in/reader035/viewer/2022062803/56649f1e5503460f94c35972/html5/thumbnails/10.jpg)
Tolerogenic role of Tolerogenic role of PD-1/PD-L1PD-1/PD-L1
PD-1 blocking Ab (RMP1-14)
ovalbumin expressing LLC cell line
ns
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• 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 laboratory
ConclusionConclusion
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AcknowledgementsAcknowledgements
Thoracic Immunology Lab
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![Page 14: CD8+ T Cells Contribute to Lung Cancer Progression in a PD-1 Dependent Fashion Stephanie Chang, Saeed Arefanian, Ryuji Higashikubo, Daniel Kreisel, Andrew.](https://reader035.fdocuments.in/reader035/viewer/2022062803/56649f1e5503460f94c35972/html5/thumbnails/14.jpg)
B6 B6 CD8-/-
106 Lewis Lung Carcinoma, B16 melanoma, EG7 Lymphoma expressing ovalbumin