Tumor microenvironment and immunotherapy of oral cancer

Abstract

Oral cancer is one of the most common malignant tumors of the head and neck, not only affects the appearance, but also affects eating and even endangers life. The clinical treatments of oral cancer mainly include surgery, radiotherapy, and chemotherapy. However, unsatisfactory therapeutic effect and toxic side effects are still the main problems in clinical treatment. Tumor microenvironment (TME) is not only closely related to the occurrence, growth, and metastasis of tumor but also works in the diagnosis, prevention, and treatment of tumor and prognosis. Future studies should continue to investigate the relationship of TME and oral cancer therapy. This purpose of this review was to analyze the characteristics of oral cancer microenvironment, summarize the traditional oral cancer therapy and immunotherapy strategies, and finally prospect the development prospects of oral cancer immunotherapy. Immunotherapy targeting tumor microenvironment is expected to provide a new strategy for clinical treatment of oral cancer.

Hypoxia mitigation by manganese-doped carbon dots for synergistic photodynamic therapy of oral squamous cell carcinoma

“…A manifestation of their zwitterionic characteristics, allows them to be well dispersed in aqueous solutions ( Zhang et al, 2015 ; Zhu et al, 2022 ). In addition, the peak at 607 cm-1 corresponding to the Mn-O functional group and a new distinct peak at around 1,220 cm-1 caused by metal-ligand stretching vibrations furthermore indicates the existence of Mn ( Liu et al, 2022 ; Dong et al, 2022 ). The results of ζ potential, XPS, XRD and FT-IR all demonstrate that Mn has been successfully doped into CDs, while the presence of a large number of hydrophilic functional groups on the surface of Mn-CDs improves the biocompatibility of the material itself.…”

“…Photodynamic therapy (PDT), which uses photosensitizers (PSs) to convert surrounding oxygen molecules into cytotoxic reactive oxygen species (ROS) under specific laser irradiation has been a minimally invasive treatment with high specificity, negligible drug resistance and few side effects that have been rapidly developed in the past decade ( Yang et al, 2018 ). However, oxygen dependence limits its application within solid tumors ( Liu et al, 2022 ; Zhang et al, 2022 ). Hypoxia is an important feature of the tumor microenvironment, usually caused by tumor cell proliferation and abnormal angiogenesis, which would limit the production of ROS and greatly reduce the efficacy of PDT ( Anderson and Simon, 2020 ; Wei et al, 2021 ).…”

“…For example, MnO 2 nanoparticles and MnO 2 -containing nanoparticles, which are widely studied, can react with H 2 O 2 and H + in TME to generate large amounts of oxygen in situ to overcome the tumor hypoxic environment and improve the efficacy of PDT, and change the pH by redox reaction with acidic H 2 O 2 in TME ( Tao et al, 2022 ). However, the current construction of nanodrug systems for PDT therapy based on manganese dioxide suffer from the following limitations: 1) the preparation process is complicated and cumbersome; 2) the drug or PSs needs to be loaded on the MnO2 nanoparticles ( Liu et al, 2022 ). Therefore, there is still a great need to establish a simple method to prepare manganese-based nanodrug.…”

The Role of Different Immunocompetent Cell Populations in the Pathogenesis of Head and Neck Cancer—Regulatory Mechanisms of Pro- and Anti-Cancer Activity and Their Impact on Immunotherapy

“…Promise is also offered by DC-based vaccination including targeting DCs in vivo with cytokines, such as GM-CSF, and agonistic antibodies, such as CD40, as well as antigens that bind to C-type lectin receptors (CLRs), such as DEC-205. Ex vivo approaches can also be used, by inducing the immature DCs originating from the patients’ monocytes into mature DCs by loading peptide, protein or tumour lysate as antigens; in addition, some approaches use nanotechnology-based immunotherapy [ 367 , 368 , 369 , 426 , 427 , 428 , 429 , 430 ]. Consequently, a key goal of immunotherapy strategies is to overcome the barriers of immune suppression or tolerance and inhibit the mechanisms that facilitate tumour escape from immune surveillance in HNSCC.…”

High 4-1BB Expression in PBMCs and Tumor Infiltrating Lymphocytes (TILs) in Patients with Head and Neck Squamous Cell Carcinoma

“…Nivolumab and cetuximab are monoclonal antibodybased therapies that target Programmed death 1 (PD-1) and EGFR, respectively. 21,22 Immunotherapy using 4-1BB is being developed for a better way of treating HNSCC, in which it is proposed to activate the anticancer immune response cells, B cells, CD4þ T cells, and CD8 þ T cells, and suppress the oncogenes. 23 The mechanism of agonistic anti-4-1BB stimulates and activates immune cells by binding with 4-1BB receptors on TILs and increasing proliferation of TILs, resulting in upregulation of an active immune response against the cancer cells.…”