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
CD8+ Memory Cells CD8+ Memory Cells Current strategies for immunotherapy focus on activation and transfer ofCD8+ cytotoxic T lymphocytes
Data from our labData from our lab
Higher Sarcoma in CD8-/- Higher Sarcoma in CD8-/-
micemiceB6 B6 CD8-/-
3-Methylcholantherene injection in flank
B6 B6 CD8-/-
Lower Lung Cancer Incidence in CD8-/- Lower Lung Cancer Incidence in CD8-/-
micemiceUrethane induction
B6 B6 CD8-/-
B6 B6 CD8-/-
106 B16 melanoma expressing ovalbumin
B6 B6 CD8-/-
106 Lewis Lung Carcinoma, B16 melanoma, expressing ovalbumin
• 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
Immunologic Immunologic PhenotypePhenotype
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
• 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
AcknowledgementsAcknowledgements
Thoracic Immunology Lab
B6 B6 CD8-/-
106 Lewis Lung Carcinoma, B16 melanoma, EG7 Lymphoma expressing ovalbumin