Abstract
Oral cavity squamous cell carcinoma (OSCC) is a common head and neck cancer characterized by a poor prognosis associated with locoregional or distant failure. Among the predictors of prognosis, a dense infiltration of adaptive immune cells is protective and associated with improved clinical outcomes. However, few tools are available to integrate immune contexture variables into clinical settings. By using digital microscopy analysis of a large retrospective OSCC cohort (n = 182), we explored the clinical significance of tumor-infiltrating CD8+ T-cells. To this end, CD8+ T-cells counts were combined with well-established clinical variables and peripheral blood immune cell parameters. Through variable clustering, five metavariables (MV) were obtained and included descriptors of nodal (NODALMV) and primary tumor (TUMORMV) involvement, the frequency of myeloid (MYELOIDMV) or lymphoid (LYMPHOIDMV) peripheral blood immune cell populations, and the density of tumor-infiltrating CD8+ T-cells (TI-CD8MV). The clinical relevance of the MV was evaluated in the multivariable survival models. The NODALMV was significantly associated with all tested outcomes (p < 0.001), the LYMPHOIDMV showed a significant association with the overall, disease-specific and distant recurrence-free survival (p < 0.05) and the MYELOIDMV with the locoregional control only (p < 0.001). Finally, TI-CD8MV was associated with distant recurrence-free survival (p = 0.029). Notably, the performance in terms of survival prediction of the combined effect of NODALMV and immune metavariables (LYMPHOIDMV, MYELOIDMV and TI-CD8MV) was superior to the TNM stage for most of the outcomes analyzed. These findings indicate that the analysis of the baseline host immune features are promising tools to complement clinical features, in stratifying the risk of recurrences.
Highlights
Oral cavity squamous cell carcinoma (OSCC) is one of the most frequent head and neck tumors [1] with a rising incidence in the Western countries [2,3]
In addition to novel histological features [15,16] and morphology-based immune contexture parameters [17], recent meta-analysis showed that, in OSCC, a favorable overall outcome is associated with a high density of tumor infiltrating lymphocytes (TIL) as NK-cells, CD45RO+ T-cells and CD8+ T-cells, mainly if measured in the tumoral site [18,19], whereas tumor-associated CD68+ or CD163+ macrophages predict a worse prognosis [19]
Considering already imputed data (Table 1), the cohort was well balanced among all pT categories, and metastatic lymph-node involvement was recorded in 85 cases (46.7%), and in 42 cases (23.1%), evidence of pathologic extranodal extension was observed
Summary
Oral cavity squamous cell carcinoma (OSCC) is one of the most frequent head and neck tumors [1] with a rising incidence in the Western countries [2,3]. Despite achieving early diagnosis, OSCC is characterized by a poor prognosis when locoregional or distant failure occurs [7], including the mandatory management of the neck with elective node dissection [8] or sentinel node biopsy [9] for low-stage tumors. In addition to novel histological features [15,16] and morphology-based immune contexture parameters [17], recent meta-analysis showed that, in OSCC, a favorable overall outcome is associated with a high density of tumor infiltrating lymphocytes (TIL) as NK-cells, CD45RO+ T-cells and CD8+ T-cells, mainly if measured in the tumoral site [18,19], whereas tumor-associated CD68+ or CD163+ macrophages predict a worse prognosis [19]. Few attempts have been made to combine peripheral and tumoral immune-features in a unique classifier [25]
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