Immunomodulatory aspects in the progression and treatment of oral malignancy

Abstract

Inflammation substantially affects the risk of oral malignancy. Pro-inflammatory cytokine, interferon (IFN)-γ, confers anti-tumor activity using several different mechanisms. Conversely, higher expression of interleukin (IL)-17 is associated with worse prognosis. Monocyte chemotactic protein (MCP)-1 correlates positively with poor long-term survival of head and neck squamous cell carcinoma (HNSCC) patients. IL-1α affects cancer associated fibroblasts and macrophages, and promote several malignant phenotypes including immune suppression. Some anti-inflammatory cytokines, including IL-10 and transforming growth factor (TGF)-β, relate to pro-tumoral activities.Among immune checkpoint modulators, programmed death (PD-)1 and PD-ligand (L)1 facilitate oral squamous cell carcinoma (OSCC) cell evasion from immune surveillance, and the expression status of these has a prognostic value.OSCCs contain tumor associated macrophages (TAMs) as major stromal cells of their tumor microenvironment. Among the two distinctive states, M2 macrophages support tumor invasion, metastasis and immune suppression. Crosstalk between TAMs and OSCC or cancer-associated fibroblasts (CAF) plays an important role in the progression of OSCC.Clinical trials with blocking antibodies against IL-1α or melanoma-associated antigens have been reported as therapeutic approaches against OSCCs. The most promising approach activating antitumor immunity is the blockade of PD-1/PD-L1 axis. Manipulating the polarization of pro-tumorigenic macrophages has been reported as a novel therapeutic approach.

Macrophages in Oral Carcinomas: Relationship with Cancer Stem Cell Markers and PD-L1 Expression

“…We speculate that this relationship between CD163 and PD-L1 expression could be the link between inflammation and immune escape in oral carcinogenesis. OSCC can be promoted by chronic inflammation, such as that which occurs in periodontitis [ 52 ]. Furthermore, it has been shown that a trauma, including an incisional biopsy, can provide a microenvironmental stimulus that affects macrophage polarization influencing tumor biology, leading to a worse prognosis and increasing the risk of developing lymph node metastasis in OSCC [ 53 ].…”

Downregulation of CCL22 and Mutation of NOTCH1 in Tongue Squamous Cell Carcinoma Decreases Th2 Cell Recruitment and Expression to Predict Poor Clinical Outcomes

“…The progression of TSCC is affected by several factors, including gene mutation, dysregulation of long non-coding RNA, and changes in the tumor microenvironment [19][20][21].…”

Advances in research on the interaction between inflammation and cancer

“… 57 The dramatic reduction in the number of mature dendritic cells allows more monocyte precursors to be used to support the growing population of TAM2 and MDSCs. 58 Subsequently, the network of cytokines established between these immune cells enhances each other and helps maintain the number of immune cells in the tumour-promoting TME. 58 In addition, it seems that TGF-β, VEGF, hypoxia-inducible factor-1α, chemokines and inflammatory cytokines (especially Th2) are induced.…”

“… 58 Subsequently, the network of cytokines established between these immune cells enhances each other and helps maintain the number of immune cells in the tumour-promoting TME. 58 In addition, it seems that TGF-β, VEGF, hypoxia-inducible factor-1α, chemokines and inflammatory cytokines (especially Th2) are induced. 59 Cytokines are associated with tumour-induced angiogenesis, inflammation and immunosuppression.…”