Spatial Distribution of Immune Cells in Head and Neck Squamous Cell Carcinomas

Abstract

BackgroundHead and neck squamous cell carcinomas (HNSCCs) have a very moderate response rate to immune checkpoint inhibitor (ICI) treatment compared to other cancer types. Lacking predictive markers for treatment response, we analyzed the immune status of HNSCC and assessed the spatial distribution of immune cells.Materials and MethodsVia assessing hematoxylin–eosin (H&E) stains, we divided HNSCCs by the immune cell distribution in hot, cold, and excluded tumors. For each group, each with 10 tumors, we performed serial immunohistochemical (IHC) staining of the immune cell markers, checkpoint molecules, and immune regulators.ResultsThe spatial distributions were different for each immune cell type, allocating regulatory T cells (Tregs) and CD11b cells predominantly in the stroma. CD4 and CD8 cells were present either in the tumor stroma or between cancer cells. Interestingly, the expressions of PD-1 (programmed cell death 1 receptor) and PD-L1 (programmed death-ligand 1) were higher in hot tumors in comparison to cold and excluded tumors. The expression of pSMAD [indicating active transforming growth factor beta (TGF-β)] was higher in excluded tumors.ConclusionDifferent immune cell distribution patterns within tumors might be crucial for ICI treatment response since hot tumors have the highest expressions of PD-1 and PD-L1. TGF-β might be a key regulator for immune cell distribution and a promising therapeutic target that determines the formation of hot or excluded immune patterns.

Molecular Subtypes Based on Cell Differentiation Trajectories in Head and Neck Squamous Cell Carcinoma: Differential Prognosis and Immunotherapeutic Responses

“…CD8+, DCs, Natural killer immune cells) that facilitate clearance of tumor cells (46). A clinical trial indicated hot tumors have significantly higher expressions of PD-1 and PD-L1 in comparison to cold tumors, they might be more prone to immune checkpoint inhibitors treatments (47). Our results also confirmed that Cluster-C corresponds to abundant CD8+T cell infiltration and highly expressions of PD-1/PD-L1 compared to Cluster-A and Cluster-B.…”

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“…Kouckýet al demonstrated a colocalization of functionally impaired pDCs with T regs in TS and reported a selective pDC-fostered T reg expansion (44). When looking at T cell subpopulations in our HNSCC cohort, T regs represented the major T H cell subset, with their predominant stromal distribution confirming current literature (45) and may contributing to the mentioned relation of pDCs and T regs . With respect to further T H subsets, T H 1 cells were more common than T H 2 cells or T H 17 cells and significantly more frequent in IET than in TS.…”

CDK7 Predicts Worse Outcome in Head and Neck Squamous-Cell Cancer

“…However, we found significantly higher CDK7 expression in immune-infiltrated tumor tissue. Previously we described higher TPS in immune-infiltrated tumors [48]. We suppose that CDK7 might drive higher PD-L1 expression in these tumors.…”