Immunohistochemical Study of PD-1/PD-L1 Axis Expression in Oral Tongue Squamous Cell Carcinomas: Effect of Neoadjuvant Chemotherapy on Local Recurrence

Abstract

While neoadjuvant chemotherapy (NAC) for patients with oral tongue squamous cell carcinoma (OTSCC) may improve tumor microenvironment, it may lead to local immune suppression caused by residual cancer cells. The efficacy of NAC is therefore controversial. In our study, we investigated tumor microenvironments after NAC using immune checkpoint molecules, and evaluated the association between tumor microenvironments, clinicopathological factors and outcomes. We reviewed the records of 121 patients who underwent radical surgery for OTSCC between April 2001 and March 2015. Patients with a positive surgical margin and a follow up period of less than 6 months were excluded. For these patients, programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) expressions were immunohistochemically examined. The expression of PD-1 and PD-L1 were significantly associated with local recurrence in patients with OTSCC (P < 0.01 and P < 0.01, respectively). We found a significant decrease in 5-year disease specific survival rate for patients with combined PD-1+/PD-L1+ expressions (P < 0.05). In the subgroup analysis of local recurrence between the NAC treated group and those who received surgery alone, high levels of PD-1 and PD-L1 expressions were significantly found in the former, but not in the latter group. Local recurrence in the NAC-treated group may contribute to local immune suppression in OTSCC. NAC lead to local immune suppression and immune checkpoint molecules play an important role in local recurrence in patients with OTSCC who received NAC. NAC modality can't be recommended for patients with OTSCC at present.

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