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