The immune cell niche associated with oral dysplastic lesion progression to carcinoma is poorly understood. We identified T regulatory cells (Treg), CD8+ effector T cells (Teff) and immune checkpoint molecules across oral dysplastic stages of oral potentially malignant disorders (OPMD). OPMD and oral squamous cell carcinoma (OSCC) tissue sections (N = 270) were analyzed by immunohistochemistry for Treg (CD4, CD25 and FoxP3), Teff (CD8) and immune checkpoint molecules (PD-1 and PD-L1). The Treg marker staining intensity correlated significantly (p < 0.01) with presence of higher dysplasia grade and invasive cancer. These data suggest that Treg infiltration is relatively early in dysplasia and may be associated with disease progression. The presence of CD8+ effector T cells and the immune checkpoint markers PD-1 and PD-L1 were also associated with oral cancer progression (p < 0.01). These observations indicate the induction of an adaptive immune response with similar Treg and Teff recruitment timing and, potentially, the early induction of exhaustion. FoxP3 and PD-L1 levels were closely correlated with CD8 levels (p < 0.01). These data indicate the presence of reinforcing mechanisms contributing to the immune suppressive niche in high-risk OPMD and in OSCC. The presence of an adaptive immune response and T-cell exhaustion suggest that an effective immune response may be reactivated with targeted interventions coupled with immune checkpoint inhibition.

The study objective was to assess if the extent of neck dissection among patients who receive adjuvant radiotherapy affects regional recurrence and survival. This was a retrospective study of patients who had clinical metastatic mucosal primary squamous cell carcinoma (SCC) to cervical lymph nodes done at Roswell Park Comprehensive Cancer Center, Buffalo, New York from 2004 to 2015. Patients with previous radiotherapy and/or chemotherapy were excluded. All patients had surgery to the primary tumor and the neck followed by adjuvant (chemo) radiation. Patients have been divided into 2 groups according to type of neck dissection as either selective neck dissection (SND) or comprehensive neck dissection (CND). The extent of neck dissection was determined by surgeon preference. All patients received postoperative radiotherapy to the primary tumor bed and to the neck with or without chemotherapy. Main outcomes were measured in regional recurrence and overall survival. In our study, 74 patients were included. Among the 2 groups of patients, 3-year outcomes for regional recurrence occurred in 4 (7.1%) of 56 patients in the SND group and 2 (11.1%) of 18 patients in the CND group. Overall survival was 29 (51.8%) of 56 patients in the SND group and 11 (61.1%) of 18 patients in the CND group (P ¼ .497). Among patients who died in each cohort, disease-specific death was 20 (74.1%) of 27 patients in the SND group and 5 (71.4%) of 7 patients in the CND group (P ¼ .79).The overall and disease-specific survival differences between the SND and CND cohorts were not statistically significant. In conclusion, SND, combined with proper adjuvant treatment, achieved regional control and survival rates comparable to CND.