PD-1/PD-L1 biology and immunotherapy in HPV-positive oral cancers

Abstract

Keywords• HPV • immune check points • immunotherapy • oral cancers • PD/PDL-1 HPV-infection related oral cancers are on the rise [2]. Conventional therapies (surgery, radiation and prophylactic vaccines) and some proposed nonconventional therapies (natural and synthetic antioxidants)-based treatments have limitations. In the light of recent advancement of immune checkpoints and their inhibitor molecule related cancer immunotherapies, we present updated information on the current status of PD-1/PD-L1 therapies in HPV mediated oral carcinogenesis. We limit the scope to oral carcinogenesis.Oral squamous cell carcinoma is the sixth most common cancer that accounts for almost 5% of all malignancies worldwide [1,2]. It is predominately attributed to smoking and alcohol, but a subset has been demonstrated to contain anogenital HPV infections. Many studies have established that the high-risk HPVs, especially HPV type 16 (HPV16) are etiologically related to a subset of oral cancer cell [1][2][3]. Nonsmokers with less median age, harboring wild type p53 and wild type p16, well-differentiated epithelium and better survival/good prognosis are some of the best identified exclusive characteristic features of HPV infected oral cancers. After surgical options and radiation therapies in platinum-refractory oral cancers, traditionally EGFR-based monoclonal antibodies are preferred by clinicians as a standard treatment regimen. But as usual, nonspecific targeting has been identified as one of the major problems, warranting the need for newer approaches such as checkpoint inhibitor-based immunotherapies.Even after four decades of HPV research, there are no specific therapies available for the effective treatment of HPV. However, virus-like particle (the major HPV virion protein L1)-based two prophylactic vaccines: quadrivalent Gardasil (HPV16/18/6/11) and bivalent Cervix (HPV16/18) are available. In 2014, the US FDA has approved a nonavalent vaccine against nine HPV types ( HPV6,11,16,18, 31, 33, 45, 52 and 58) but these vaccines are not commercialized well in developing countries [4][5][6].

Role of Molecular Targeted Therapeutic Drugs in Treatment of Oral Squamous Cell Carcinoma: Development and Current Strategies—A Review Article

“…Their coexpression was analogous to the prognosis of different malignant tumors such as melanoma and OSCC. 8 9 Presently, two drugs are used to target PD-1. They are nivolumab and pembrolizumab.…”

Application of Macro-Synthetic-Fiber-Reinforced Sprayed Concrete for Primary Lining Support on Highway Tunnel Project in Bosnia and Herzegovina

“…The top heading, bench and the invert arch excavation phase. In better underground conditions the excavation works were divided in top heading and bench phases only [3]. The Main Design defined rock categories, predicting the round lengths and defining support elements (system) for each of the rock category respectively (Table 1).…”

Expression of the Programmed Death Ligand (PDL-1) CD274 in Oral Squamous Cell Carcinomas

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BackgroundB7-H1 (also known as programmed death ligand or PDL-1) is an inhibitory molecule of T cells implicated in the protection of tumor cells from immune targeting [1,2]. Recent evidence has suggested some proportion of squamous cell carcinomas of the head and neck (SCCHN) expressed B7-H1, which has also been reported in breast, cervical, esophageal and colorectal cancers [3,4]. B7/PDL-1 binds the cognate receptor programmed death (PD-1) on cytotoxic T-cells, which leads to apoptosis and thus protection from lysis by activated T-cell (CTL) surveillance [5,6].Although several studies have reported screening for B7-H1 or PDL-1 among clinical patient samples, few if any have evaluated whether this expression is found among well-characterized oral cancer cell lines [7,8].

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