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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE163131 | GEO | 2021/03/09

REPOSITORIES: GEO

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Project description:All nucleated mammalian cells express major histocompatibility complex (MHC) proteins that present peptides on cell surfaces for immune surveillance. These MHC-presented peptides (pMHC) can convey non-self antigens derived from pathogens or mutations to amount T-cell responses. Alterations in tumor-specific antigens – particularly mutation-bearing peptides (neoantigens) presented by MHC — can serve as potent substrates for anti-tumor immune responses. Here we employed an integrated genomic and proteomic antigen discovery strategy aimed at measuring interferon gamma (IFN-γ) induced alterations to antigen presentation, using a lymphoma cell line. IFN-γ treatment resulted in a set of differentially expressed proteins (2 % of all quantified proteins) including components of antigen presentation machinery or interferon signaling pathways. In addition, several proteasome subunits were found to be modulated, consistent with previous reports of immunoproteasome induction by IFN-γ exposure. This finding suggests that a modest proteomic response to IFN-γ could create larger alteration to cells antigen repertoires. Accordingly, by surveying immunopeptides, distinct peptide repertoires were exclusively observed in the IFN-γ induced samples. Furthermore, an additional set of presented peptides distinguished control and the IFN-γ samples by their altered relative abundances including neoantigens. Accordingly, we developed a classification system to distinguish peptides which are differentially presented due to altered expression from novel peptides resulting from changes in antigen processing. Taken together, these data demonstrate that IFN-γ can re-shape antigen repertoires by identity and by abundance. Extending this approach to models with greater clinical relevance should help develop strategies by which immunopeptide repertoires are intentionally reshaped to improve endogenous or vaccine-induced anti-tumor immune responses and potentially anti-viral immune responses.

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

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