IL-1/IL-1R Signaling in Head and Neck Cancer.

Sven E Niklander,Keith D Hunter,Craig Murdoch

doi:10.3389/froh.2021.722676

Abstract

Decades ago, the study of cancer biology was mainly focused on the tumor itself, paying little attention to the tumor microenvironment (TME). Currently, it is well recognized that the TME plays a vital role in cancer development and progression, with emerging treatment strategies focusing on different components of the TME, including tumoral cells, blood vessels, fibroblasts, senescent cells, inflammatory cells, inflammatory factors, among others. There is a well-accepted relationship between chronic inflammation and cancer development. Interleukin-1 (IL-1), a potent pro-inflammatory cytokine commonly found at tumor sites, is considered one of the most important inflammatory factors in cancer, and has been related with carcinogenesis, tumor growth and metastasis. Increasing evidence has linked development of head and neck squamous cell carcinoma (HNSCC) with chronic inflammation, and particularly, with IL-1 signaling. This review focuses on the most important members of the IL-1 family, with emphasis on how their aberrant expression can promote HNSCC development and metastasis, highlighting possible clinical applications.

Highlights

The association between chronic inflammation and cancer has been reported for many years
Interleukin-1 (IL-1) is commonly found at tumor sites and is considered one of the most important cytokines of the tumor microenvironment (TME), where it plays a key role in carcinogenesis and tumor progression [6], and its expression has been associated with poor prognosis in cancer patients [7]
Cumulating evidence suggests that the effects of IL-1 autocrine and paracrine signaling within the TME is central to head and neck squamous cell carcinoma (HNSCC) development

Summary

INTRODUCTION

The association between chronic inflammation and cancer has been reported for many years. IcIL-1RA1 would block an upstream kinase in the p38 MAPK or NF-κB pathways, indirectly inhibiting p38 MAPK or NFκB phosphorylation and its downstream products, such as IL-6 and CXCL8 [91] It can be hypothesized that downregulation of icIL1RA in HNSCC could lead to de-regulated expression of pro-inflammatory cytokines related to cancer development by allowing the un-controlled activation of IL-1α and NF-κB (Figure 3). This speculation is based on the finding that OSCC constitutively express higher levels of IL-1α and NFκB than healthy controls [8, 100, 118, 141] and that levels of IL-6 and CXCL8 are elevated in OSCC [142, 143]. This is of importance as HNSCC cells are able to secrete IL-1β which stimulates other cells of the TME (such as fibroblasts) to generate chemokines and other inflammatory molecules creating an inflammatory TME with cancer promoting properties [11]

Utility as a Saliva Biomarker

CONCLUSION