Evaluation of the Immune Microenvironment in Sinonasal Squamous Cell Carcinoma and Its Association with Patients' Survival

Background: Sinonasal squamous cell carcinoma (SNSCC) is the most common type of sinonasal cancer. Despite improvements in surgery, radiotherapy, and systemic therapy, the prognosis is still poor. Therefore, there is a need for new therapeutic options for SNSCC treatment, including immunotherapy. The aim of this study was to evaluate the signature of the tumor immune microenvironment and analyze its correlation with clinical outcomes in SNSCC.

Materials and Methods: SNSCC tumor samples obtained from 53 patients were used in this study. All the patients were treated and underwent surgical resection at MD Anderson Cancer Center and the median follow-up period was 41.5 months (range: 6.4–166.9 months). Multiplex immunofluorescence for pan-cytokeratin (CK, used as a tumor marker), CD4, CD8, CD20, CD68, forkhead box P3 (FOXP3), lymphocyte-activation gene 3, and programmed death-ligand 1 (PD-L1) was performed. The immune infiltration score was defined as the ratio between immune cells and CK+ cells. Overall survival (OS) and disease specific survival (DSS) status were assessed by t-test, and the survival rate differences were calculated using log-rank test.

Results: The median of the immune infiltration score across all tumor samples was 0.35, indicating high immunogenic characteristics of SNSCC. The following markers showed significant association with favorable survival status; low CK+PD-L1+ was associated with OS (p = 0.0341), high CD8+ was associated with OS and DSS (p = 0.0423 and 0.008, respectively), high CD4+FOXP3+ was associated with OS (p = 0.0175) and high CD68+PD-L1 was associated with DSS (p = 0.0292). Among these markers, CD8 expression was found to be associated with five-survival rates by the Kaplan–Meier analysis; patients with higher CD8+ expression had a trend toward better OS (probability of survival, CD8+ high 68.6% vs. CD8+ low 41.2%, p = 0.077) and significant better DSS (probability of survival: CD8+ high 56% vs. CD8+ low 36%, CD8+ high, p = 0.0459).

Conclusions: Our study showed that high expression of CD8 was associated with better survival rate in patients with SNSCC. Considering favorable survival status in tumor cells with low expression of PD-L1 patients, stimulating CD8 combined with PD-L1 inhibition might be a potential therapeutic target for the treatment of SNSCC.

Publication History

Article published online:
12 February 2021