Plasticity of PD-L1 expression between nodal metastases and primary tumors in p16 negative squamous cell carcinoma of the oral cavity

Abstract

Background: the recent achievements of immunotherapy in many different areas (melanoma, kidney, lung and bladder carcinoma) stimulate the investigation about the action of check points inhibitors in other tumors, particularly in case of tumors with an high mutational load, that are potentially responsive to immunotherapy approaches, like p16 negative oral squamous cell carcinoma. Phase III studies are ongoing, and there are also preliminary data about the PD-L1 tissue expression, in correlation with tumor grade and stage. However, investigations concerning the possible up/down regulation of this ligand in primary vs nodal metastasis are still largely inadequate. Material and methods: 16 oral squamous cell carcinoma T2-T4, node positive (N1), p16 negative, moderately differentiated (G2), underwent immunostaining with anti PD-L1 rabbit MoAb SP 142, using a VENTANA BenchMark Ultra platform with OptiView detection kit. Both primary tumors and nodal metastases were immunostained. Results were evaluated according to Roche PD-L1 (SP142) scoring system. In particular, neoplastic cell immunoreactivity (TC) and immune cells (lymphocytes, macrophages, dendritic cells and granulocytes) intratumoral and peritumoral immunoreactivity (IC) were evaluated. CD3 immunostaing of both primary tumors and nodal metastases were also performed, in order to facilitate the interpretation of the results. Results: the entire group of 16 cases showed PD-L1 expression in perineoplastic IC, ranging from 1% to 50%, according to the scoring. No significant variations of expression between primary and secondary nodal sites were observed in all cases but one. Conversely, 10 out of 16 showed no expression of PD-L1 on TC (0%) both in primary tumor and nodal metastasis. The other six cases showed: case 4: T 0%, N 60%; case 5: T 80%, N 5%; case 6: T 70%, N 5%, case 11: T 50%, N 0%; case 13: T 30%, N 10%, case 16: T 40%, N 1%. Conclusions: in the light of the relevance of PD-L1 expression in term of immunotherapy efficacy in other areas (lung and bladder carcinoma), this documented plasticity (37.5% of cases) might be an interesting information for future trials.