Lachnoclostridium and Immune Inflamed Gene Expression Signature Association in Head & Neck Cancers

Purpose/Objective(s)

The immune microenvironment plays an essential role in the progression of head and neck squamous cell carcinoma (HNSCC). The association of the tumor microbiota and immune microenvironment is not well defined. The Cancer Genome Atlas Project (TCGA) analysis provided the diversity of microbiota in different cancer types. We analyzed the TCGA microbiome database to better understand the role of the tumor microbiome in HNSCC.

Materials/Methods

Human papillomavirus (HPV) positive and HPV negative HNSCC samples in the TCGA database were analyzed. Data were accessed using cBioPortal. Spearman's test was used to correlate Lachnoclostridium microbiome signature with immune-related gene expressions.

Results

Microbiome signatures were compared in PDL1 low and PDL1 high HNSCC. Lachnoclostridium was among the top genus enriched in the PDL1 high expression group in both HPV+ and HPV- HNSCC. Lachnoclostridium was correlated with immune inflamed gene expression profile. To evaluate the differential gene expressions in Lachnoclostridium enriched HNSCC, the gene expression profile of Lachnoclostridium high and low HNSCC samples were compared. MHC class I genes; HLA-A, HLA-B, HLA-C, HLA-E, HLA-F, TAP1, and TAP2 were among the top differentially expressed genes. Then we evaluated the correlation of MHC-I genes with Lachnoclostridium enrichment. Lachnoclostridium signature was significantly correlated with expression of these MHC I genes, with Spearman's correlation coefficient ranging between 0.51-0.59.

Conclusion

Lachnoclostridium is a recently defined genus found in the human gut microbiome. Here we, for the first time, identify the enrichment of this genus in high PDL1 expressing HNSCC. The association of Lachnoclostridium signature with the immune inflamed gene expression profile and MHC-I gene signature suggests its potential role in modulating the immune microenvironment in HNSCC.