Abstract
Background: Recruiting regulatory CD4 T cells (Tregs) into the tumor microenvironment is an important tumor escape mechanism. Diminishing these suppressive cells is therefore one of the targets of cancer immunotherapy. Selective depletion of Tregs has proven successful in enhancing anti-tumor immunity and therapeutic efficacy in multiple tumor types. However, the role of Tregs in oral/oropharyngeal cancers is unclear with conflicting evidence regarding the effect of these suppressive cells on tumor prognosis. In this study, we sought to review the role of Tregs in oral/oropharyngeal cancer with the aim of deciphering the controversy regarding their effect on tumor progression and prognosis.Methods: A systematic review of the literature pertaining to the role of Tregs in oral/oropharyngeal cancer was performed using Scopus, Embase, and PubMed. Forty-five records were deemed eligible and data describing methodology of Treg detection, tumor type, and association with prognosis were extracted.Results: Of the 45 eligible manuscripts accepted for this systematic review, thirty-nine studies reported data from human subjects while the remaining studies focused on animal models. Sixteen studies were carried out using peripheral blood samples, while samples from the tumor site were analyzed in 18 studies and 11 studies assessed both blood and tumor samples. The transcriptional factor, Foxp3, was the most commonly used marker for Treg identification (38/45). The findings of 25 studies suggested that an increase in Tregs in the tumor microenvironment and/or peripheral blood was associated with poorer prognosis. These conclusions were attributed to the suppression of immune responses and the consequent tumor progression. Conversely, nine studies showed an increase in Tregs in peripheral blood and/or tumor microenvironment was related to a favorable prognosis, particularly in the presence of human papilloma virus (HPV), the status of which was only assessed in 11 studies.Conclusions: This review underlines the importance of host immunity in the behavior of oral/oropharyngeal cancer. Furthermore, we report an apparent lack of clarity regarding the true role Tregs play in oral/oropharyngeal cancer progression which could be attributed to inconsistent detection techniques of Tregs. Our results therefore highlight the need for clearer methodologies and more robust phenotyping when defining Tregs.
Highlights
Head and neck cancer is the sixth most common malignancy with an estimated 686,000 new cases and 375,000 deaths reported annually (1)
Along with alcohol consumption, smoking and various forms of betel quid chewing [which have long been associated with the development of oral and oropharyngeal squamous cell carcinoma (OPSCC)], it is recognized that human papilloma virus (HPV) infection plays an important role in the onset of HPV positive OPSCC (2)
Reasons for exclusion included irrelevant manuscripts which did not tackle the role of Tregs in oral and oropharyngeal cancer (n = 478), manuscripts that focused on tumors other than oral or oropharyngeal; laryngeal/esophageal (n = 82), salivary gland (n = 44), thyroid gland (n = 32) or gastric tumors (n = 18), review articles (n = 13), one study looked at the role of Tregs in periodontal disease and two articles were excluded because they assessed the expression of Foxp[3] in tumor cells rather than assessing Tregs
Summary
Head and neck cancer is the sixth most common malignancy with an estimated 686,000 new cases and 375,000 deaths reported annually (combined worldwide laryngeal, oral, and pharyngeal cancer incidence) (1). Despite advances in diagnosis and treatment, OPSCC mortality rate has improved little over the years, with 5 year survival rates as low as 53% reported in England for cancers of the oral cavity (3). Despite the impressive successes in cancer immunotherapy, the response in patients is sometimes short lived This is due to factors that hamper the immune response against cancer such as the presence of the suppressive regulatory CD4 T cells (Tregs) in the tumor microenvironment (5). Recruiting regulatory CD4 T cells (Tregs) into the tumor microenvironment is an important tumor escape mechanism Diminishing these suppressive cells is one of the targets of cancer immunotherapy. We sought to review the role of Tregs in oral/oropharyngeal cancer with the aim of deciphering the controversy regarding their effect on tumor progression and prognosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
