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Over the past few decades, tremendous advances in the prevention, diagnosis, and treatment of cancer have taken place. However for head and neck cancers, including oral cancer, the overall survival rate is below 50% and they remain the seventh most common malignancy worldwide. These cancers are, commonly, aggressive, genetically complex, and difficult to treat and the delay, which often occurs between early recognition of symptoms and diagnosis, and the start of treatment of these cancers, is associated with poor prognosis. Cancer development and progression occurs in concert with alterations in the surrounding stroma, with the immune system being an essential element in this process. Despite neutrophils having major roles in the pathology of many diseases, they were thought to have little impact on cancer development and progression. Recent studies are now challenging this notion and placing neutrophils as central interactive players with other immune and tumor cells in affecting cancer pathology. This review focuses on how neutrophils and their sub-phenotypes, N1, N2, and myeloid-derived suppressor cells, both directly and indirectly affect the anti-tumor and pro-tumor immune responses. Emphasis is placed on what is currently known about the interaction of neutrophils with myeloid innate immune cells (such as dendritic cells and macrophages), innate lymphoid cells, natural killer cells, and fibroblasts to affect the tumor microenvironment and progression of oral cancer. A better understanding of this dialog will allow for improved therapeutics that concurrently target several components of the tumor microenvironment, increasing the possibility of constructive and positive outcomes for oral cancer patients. For this review, PubMed, Web of Science, and Google Scholar were searched for manuscripts using keywords and combinations thereof of “oral cancer, OSCC, neutrophils, TANs, MDSC, immune cells, head and neck cancer, and tumor microenvironment” with a focus on publications from 2018 to 2021.

Antimicrobial peptides (AMPs) are found in nearly all living organisms, show broad spectrum antibacterial activity, and can modulate the immune system. Furthermore, they have a very low level of resistance induction in bacteria, which makes them an ideal target for drug development and for targeting multi-drug resistant bacteria ‘Superbugs’. Despite this promise, AMP therapeutic use is hampered as typically they are toxic to mammalian cells, less active under physiological conditions and are susceptible to proteolytic degradation. Research has focused on addressing these limitations by modifying natural AMP sequences by including e.g., d-amino acids and N-terminal and amino acid side chain modifications to alter structure, hydrophobicity, amphipathicity, and charge of the AMP to improve antimicrobial activity and specificity and at the same time reduce mammalian cell toxicity. Recently, multimerisation (dimers, oligomer conjugates, dendrimers, polymers and self-assembly) of natural and modified AMPs has further been used to address these limitations and has created compounds that have improved activity and biocompatibility compared to their linear counterparts. This review investigates how modifying and multimerising AMPs impacts their activity against bacteria in planktonic and biofilm states of growth.

The tumor microenvironment (TME) is known to have a strong influence on tumorigenesis, with various components being involved in tumor suppression and tumor growth. A protumorigenic TME is characterized by an increased infiltration of tumor associated macrophages (TAMs), where their presence is strongly associated with tumor progression, therapy resistance, and poor survival rates. This association between the increased TAMs and poor therapeutic outcomes are stemming an increasing interest in investigating TAMs as a potential therapeutic target in cancer treatment. Prominent mechanisms in targeting TAMs include: blocking recruitment, stimulating repolarization, and depletion methods. For enhancing targeting specificity multiple nanomaterials are currently being explored for the precise delivery of chemotherapeutic cargo, including the conjugation with TAM-targeting peptides. In this paper, we provide a focused literature review of macrophage biology in relation to their role in tumorigenesis. First, we discuss the origin, recruitment mechanisms, and phenotypic diversity of TAMs based on recent investigations in the literature. Then the paper provides a detailed review on the current methods of targeting TAMs, including the use of nanomaterials as novel cancer therapeutics.