Neoadjuvant immunotherapy of oral squamous cell carcinoma modulates intratumoral CD4/CD8 ratio and tumor microenvironment: a multicenter phase II clinical trial.

PURPOSE: To investigate the clinicopathologic effects of local neoadjuvant Leukocyte Interleukin Injection (LI) regimen in oral squamous cell carcinoma (OSCC) patients. Treatment regimen included LI 800 IU/d as interleukin-2 (IL-2), administered half peritumorally and half perilymphatically five times per week for 3 weeks; low-dose cyclophosphamide; indomethacin; zinc; and multivitamins. PATIENTS AND METHODS: Thirty-nine patients diagnosed with T2-3N0-2M0 OSCC participated in the pathology portion of this phase II multicenter study (19 LI-treated patients and 20 historical controls). Clinical responses were determined by imaging. Paraffin-embedded tumor samples were obtained at surgery for all patients. Surgery for the LI-treated group was performed between days 14 and 54 after the end of treatment. Histologic evaluation, pathologic staging, necrosis, and American Joint Committee on Cancer grading were performed from hematoxylin and eosin sections. Immunohistochemistry and morphometry determined cellular infiltrate. RESULTS: Two pathologically complete, two major (> 50%), and four minor responses (> 30% but < 50%) resulted from LI treatment (overall response rate, 42%). Histopathology showed that the intratumoral CD4+:CD8+ ratio was low (< 1) in patients not treated with LI (controls). An increase in tumor-infiltrating CD4+ and a decrease of CD8+ T cells was observed in LI-treated patients, leading to a significantly (P < .05) higher intratumoral CD4+:CD8+ ratio (> 2.5). This was paralleled by dendritic cell transition from tumor surface toward stromal interface (P < .05), with macrophage decrease and neutrophil accumulation, multifocal microscopic necrosis, and significant (P < .05) increase in tumor stroma of LI-treated patients compared with controls. CONCLUSION: LI-treated OSCC patients were characterized by a markedly altered composition of tumor-infiltrating mononuclear cells, increased CD4+:CD8+ ratio, and increased tumor stroma to epithelial ratio, all of which were distinct from controls.

Considerations in the treatment of the node-negative (N0) neck in glottic carcinomas.

Treatment of lymph node negative (N0) glottic carcinoma has raised numerous controversy for decades. Prevention is one of the oldest axioms in medicine. On the other hand, overtreatment can cause unnecessary harm to patients. This retrospective study was performed in 206 patients having glottic cancers with clinically node-negative (N0) necks. The aim of this assessment is to deal with the diagnosis, predictive factors and surgical therapy of occult metastases of squamous cell cancers originating from the glottic region. The examinations were performed in three phases. Preoperative clinical, histological - and in selective cases - imaging were carried out to separate high-risk patients. Intraoperative cases of open surgery after U-shaped skin preparation up to the hyoid bone with direct inspection of jugular lymph node chain (JLNCh) where the neck was staged. The enlarged suspicious nodes were submitted for immediate frozen section. The types of neck dissection were based on the size, shape, number and histological diagnosis of regional nodes. The postoperative additional management was decided according to the results of definitive pathological findings from serial sections of the dissected specimen. Endolaryngeal LASER surgery was carried out in 87 patients based on clinical, histological and imaging criteria. In the course of two years follow-up 2 occult metastases became clinically apparent. At 119 cases open surgery were performed. In 51 patients we could not see enlarged lymph nodes (N< 2 mm) with direct examination, and thus the JLNCh remained intact. In 68 patients elective neck dissections (END) were carried out. In cases of extracapsular spread (ECS) and/or multiple nodal involvements additional radiotherapy was given.