The ‘Danse Macabre’—Neutrophils the Interactive Partner Affecting Oral Cancer Outcomes

Abstract

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.

β-Lapachone promotes the recruitment and polarization of tumor-associated neutrophils (TANs) toward an antitumor (N1) phenotype in NQO1-positive cancers

“… 35 Additionally, there are numerous reports indicating that anti-tumor N1 neutrophils within the TME release a range of alarmins, chemokines, and cytokines, which not only facilitate DC recruitment to the TME but also play crucial roles in the maturation and activation of DCs, thereby initiating anti-tumor adaptive immunity. 59 Our RT-qPCR based analysis further supports the involvement of β-Lap-induced tumor-infiltrated neutrophils in DC recruitment to the tumor microenvironment through the secretion of various chemokines. Although some reports suggest that activated neutrophils might impair T cell activation and proliferation, akin to the effects of myeloid-derived suppressor cells (MDSCs), 38 the dynamics of neutrophil-T cell interactions are highly dependent on the activation states of both cell types.…”

LINC00937 acts bi-function in oral squamous cell carcinoma cell growth and immune cell infiltration regulated FGR/IL10RA axis

“…To our knowledge, B and T cells shown a major role in in clinical early-stage of OSCC (23). Neutrophils also play an important role in in uencing cancer pathology in interaction with immune and tumor cells (24). Small Extracellular Vesicles derived from oral cancer stem cells promote M2 macrophage polarization and suppress CD4 + T-cell activity (25).…”

Effects of folate deficiency and sex on carcinogenesis in a mouse model of oral cancer

“…Dysfunctional T cells associated with tumors present inhibitory cell surface receptors, such as CTLA‐4 and PD‐1, and are impaired in their abilities to produce cytokines and to proliferate (Danella et al, 2023; Wherry, 2011). Tumor‐associated N2 Neutrophils are often immunosuppressive and thus promote cancer proliferation (Hadjigol et al, 2022; Keeley et al, 2019). Potential manipulation of the tumor microenvironment has been identified as a promising new approach to head and neck cancer therapies (Ruffin et al, 2023; Xiang et al, 2023).…”

“…PD-1, and are impaired in their abilities to produce cytokines and to proliferate (Danella et al, 2023;Wherry, 2011). Tumor-associated N2 Neutrophils are often immunosuppressive and thus promote cancer proliferation (Hadjigol et al, 2022;Keeley et al, 2019).…”