PD-1 blockade attenuates immunosuppressive myeloid cells due to inhibition of CD47/SIRPα axis in HPV negative head and neck squamous cell carcinoma

Myeloid-derived suppressor cells (MDSCs) and tumor associated macrophages (TAMs) play key roles in the tumor immune suppressive network and tumor progression.However, precise roles of programmed death-1 (PD-1) in immunological functions of MDSCs and TAMs in head and neck squamous cell carcinoma (HNSCC) have not been clearly elucidated.In the present study, we show that PD-1 and PD-L1 levels were significantly higher in human HNSCC specimen than in normal oral mucosa.MDSCs and TAMs were characterized in mice and human HNSCC specimen, correlated well with PD-1 and PD-L1 expression.aPD-1 treatment was well tolerated and significantly reduced tumor growth in the HNSCC mouse model along with significant reduction in MDSCs and TAMs in immune organs and tumors.Molecular analysis suggests a reduction in the CD47/SIRPa pathway by PD-1 blockade, which regulates MDSCs, TAMs, dendritic cell as well as effector T cells.Hence, these data identify that PD-1/PD-L1 axis is significantly increased in human and mouse HNSCC.Adoptive aPD-1 immunotherapy may provide a novel therapeutic approach to modulate the micro-and macro-environment in HNSCC.