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American Head & Neck Society
Annual Meeting, April 10-11, 2013
JW Marriott Grande Lakes
Orlando, Florida

During the
Combined Otolaryngology Spring Meeting
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EXPRESSION PROFILE AND IN VITRO BLOCKADE OF PD-1/PD-L1 IN PATIENTS WITH HEAD AND NECK SQUAMOUS CELL CARCINOMA

Presentation: P001
Topic: Basic Science - Immunology
Type: Poster
Date: Wednesday - Thursday, April 10 - 11, 2013
Session: Designated Poster viewing times
Authors: Ian-James Malm, Tullia C Bruno, PhD, Mikhail Gorbounov, BA, Janis Taube, MD, Charles Drake, MD, PhD, Young Kim, MD, PhD
Institution(s): Johns Hopkins Medical Institutions

Background:
Targeting PD-1/PD-L1 immune checkpoint signaling with a blocking αPD-1 antibody showed efficacy in a recent clinical trial for advanced melanoma, lung cancer, and renal carcinoma. In this trial, the expression of PD-L1 on tumor specimen was found to be a critical biomarker, correlating with the clinical efficacy of PD-1 blockade. However, the expression profile of PD-1/PD-L1 and the potential of PD-1 blockade in non-HPV head and neck squamous cell carcinoma (HNSCC) patients have not been explored in detail.

Methods:
We harvested CD4+ and CD8+ T cells from the peripheral blood (PBL), draining lymph nodes (DLN) and tumor (TIL) of non-HPV HNSCC patients undergoing surgical ablation treatment. These lymphocytic cells were phenotyped via flow cytometry for PD-1, and its functional activity was assessed with a mixed lymphocyte reaction (MLR) using blocking αPD-1 treatment. Furthermore, we characterized the expression profile of the PD-1 ligand, PD-L1, on HNSCC tumor samples using immunohistochemistry.

Results:
FACS analysis revealed significantly increased PD-1 expression on CD4+ and CD8+ T cells from HNSCC patients in all three compartments (PBL, DLN, and TIL), with the highest level of positivity in the TIL. There was significant enrichment of PD-1+ lymphocytes (both CD4 and CD8) in the TIL in comparison to the PBL in all the matched samples analyzed. Of note, 50-80% of tumor infiltrating CD4+ and CD8+ lymphocytes expressed PD-1. Moreover, 15-30% of circulating CD4+ and CD8+ cells expressed PD-1 in comparison to <15% in normal donors. An in vitro mixed lymphocyte reaction of the T cells from the peripheral blood and the tumor microenvironment demonstrated that PD-1 blockade could induce T cell proliferation in both CD4+ and CD8+ T cells, demonstrating the functional ability of PD-1+ cells to suppress T-cells. When we examined archived HNSCC tumor specimens, the tumor cells were found to express PD-L1.

Conclusions:
In HNSCC patients, both CD4+ and CD8+ T-cells from all three compartments expressed PD-1, with a significant enhancement of PD-1+ cells in the tumor microenvironment. Moreover, the HNSCC tumor cells expressed PD-L1, a critical biomarker of PD-1 blockade efficacy. Cumulatively, our clinical data strongly supports the introduction of αPD-1 blockade in HNSCC patients that are refractory to standard treatments.
 

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