Characterization of the immune profile of oral tongue squamous cell carcinomas with advancing disease

Abstract

We investigated whether a unique immune response was instigated with the development of oral tongue squamous cell carcinomas (OTSCC), with/without nodal involvement, with/without recurrent metastatic disease, or within tumor involved nodes. One hundred and ten formalin‐fixed paraffin‐embedded samples were collected from a retrospective cohort of 67 OTSCC patients and 10 non‐cancerous tongue samples. Targets including CD4, CD8, FOXP3, PD‐L1, and PD‐1 were analyzed by immunohistochemistry. The Nanostring PanCancer Immune Profiling Panel was used for gene expression profiling. Data were externally validated in the The Cancer Genome Atlas (TCGA) head and neck (HNSCC), melanoma and lung squamous cell carcinoma (LSCC) cohorts. A 24‐immune gene signature was identified that discriminated more aggressive OTSCC cases, and although not prognostic in HNSCC was associated with survival in other TCGA cohorts (improved survival for melanoma, P < .001 and worse survival for LSCC, P = .038). OTSCC exhibited concordant gene and immunohistochemical (IHC) features characterized by a TH‐2 biased, proinflammatory profile with upregulated B cell and neutrophil gene activity and increased CD4, FOXP3, and PD‐L1 expression (P < .001 for all by IHC). Compared to less advanced disease, nodal involvement and recurrent OTSCC did not induce a different immune response although recurrent disease was characterized by significantly higher PD‐L1 expression (P = .004 by SP263, P = .013 by 22C3, P = .004 for gene expression). Identification of a gene signature associated with different prognostic effects in other cancers highlights common pathways of immune dysregulation that are impacted by the tumor origin. The significant immunosuppressive signaling in OTSCC indicates primary failure of immune system to control carcinogenesis emphasizing the need for early, combination therapeutic approaches.

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

“…This is why, in the study presented here, we focused on IHC-based analysis to better understand the landscape of immune cells in HNSCC. In other IHC-based studies of HNSCC, the focus was on a more general description of the relation of the immune cell types rather than their spatial distribution (25,33) or on a single location such as that of oral tongue cancers (34). The study of Meehan et al included a mixture of PT and recurrent disease (RD) HNSCC of the tongue.…”

Proteomic Analysis of Circulating Extracellular Vesicles Identifies Potential Biomarkers for Lymph Node Metastasis in Oral Tongue Squamous Cell Carcinoma

“…Overall, we have shown that there are a large number of deregulated EV proteins in plasma from patients with and without nodal OTSCC compared with non-cancer controls. We highlight that this is in stark comparison with our tissue-based gene expression study which showed negligible changes in primary tissues of OTSCC with and without nodal disease and non-cancer controls [ 52 ]. Although our earlier study utilized tissues and targeted immuno-cancer genes and the current study utilized plasma and was untargeted, we expected some overlap.…”

High PD-L1 Expression on Tumor Cells Indicates Worse Overall Survival in Advanced Oral Squamous Cell Carcinomas of the Tongue and the Floor of the Mouth but Not in Other Oral Compartments

“…In other works concerning OSCC, PD-L1 expression on TCs was observed with variable frequency ranging from approximately 10 to 90% of cases [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ]. The studies differed in the size of the study group, selection of patients, antibody clones used, and the way of assessing PD-L1 expression; the two latter factors in particular significantly influence the final results of the study.…”