Soluble Sema4D in plasma as an immune biomarker of non-inflamed head and neck squamous cell carcinoma profile.

This work demonstrates the potential of soluble Semaphorin 4D (sSema4D) as an immune biomarker in plasma of patients with head and neck squamous cell carcinoma (HNSCC) that can read the histological immune subtype (HIS) and IFN-γ signature of the paired tumor tissue. Advanced analysis of 10 HNSCC tumor tissue using the IO-360 nanoString platform, showed that tumors with high sSema4D in plasma (HsS4D) clustered as negative IFN-γ immune signature and were most of histologically immune Excluded (HIS‐IE). 2/3 of the tumors with low sSema4D (LsSema4D) were IFN-γ positive, and histologically inflamed as scored using Sema4D in the tumor bed. Advanced custom analysis showed the myeloid immune cell type, Wnt and TGF-beta signaling and hypoxia to predominate in the paired tumor tissue of HsS4D, while the lymphoid compartment and costimulatory signaling was more in the low sSema4D (LsS4D) with high Treg component. Under an Institutional Review Board (IRB) approved protocol and patient consent at the University of Maryland School of Medicine (UMSOM) (HP-00073603), paired blood samples and whole excision tumor tissues were collected prospectively. Blood was drawn pre-operatively at the day of surgery. 10 samples were used for RNA extraction for nCounter Human Pan Cancer IO-360 nanoString Technology . Please note that the sample characteristics for the Age, gender and race have been updated on Nov 14, 2022.