A current limitation of the effectiveness of immunotherapies has toxic effects on the immune system in noncancerous tissues. To identify immune pathways unique to tumors, Mair and colleagues compared immune phenotypes in human head and neck squamous cell carcinomas (HNSCC) with inflamed surrounding oral mucosal tissue and with peripheral blood immune cells, using flow cytometry, single cell transcriptomics, and the NicheNet ligand-receptor analysis tool for cell-cell interactions. First, they found tremendous congruence between immune cells in tumor tissues compared with cells in inflamed nontumor tissues. Second, they discovered that IL1R1 and the previously defined marker ICOS were almost exclusively induced on tumor-infiltrating regulatory T cells (Treg). Third, they found that IL1R1+ Tregs were highly suppressive. IL1R1 was induced on Tregs acutely, therefore its expression in tumors was likely a consequence of the high activation state of Tregs in tumors. Further, Tregs expressed high levels of the chemokine receptor CXCR6....

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