Inflammation: A key process in skin tumorigenesis

Abstract

The extremely delicate shift from an inflammatory process to tumorigenesis is a field of major scientific interest. While the inflammation induced by environmental agents has well known underlying mechanisms, less is known concerning the oncogenic changes that follow an inflammatory chronic status in the tissue microenvironment that can lead to pro-tumorigenic processes. Regardless of the origin of the environmental factors, the maintenance of an inflammatory microenvironment is a clear condition that favors tumorigenesis. Inflammation sustains the proliferation and survival of malignant transformed cells, can promote angiogenesis and metastatic processes, can negatively regulate the antitumoral adaptive and innate immune responses and may alter the efficacy of therapeutic agents. There is an abundance of studies focusing on molecular pathways that trigger inflammation-mediated tumorigenesis, and these data have revealed a series of biomarkers that can improve the diagnosis and prognosis in oncology. In skin there is a clear connection between tissue destruction, inflammation and tumor onset. Inflammation is a self-limiting process in normal physiological conditions, while tumor is a constitutive process activating new pro-tumor mechanisms. Among skin cancers, the most commonly diagnosed skin cancers, squamous cell carcinoma and basal cell carcinoma (BCC) have important inflammatory components. The most aggressive skin cancer, melanoma, is extensively research in regards to the new context of novel developed immune-therapies. In skin cancers, inflammatory markers can find their place in the biomarker set for improvement of diagnosis and prognosis.

Keywords: immune cells; inflammasome; inflammation; melanoma; non-melanoma skin cancer; tumorigenesis.

Figure 1.

Relation between keratinocytes and T lymphocytes. Keratinocytes secrete upregulatory cytokines and chemokines IL-1, GM-CSF, TNF-α, IL-6, IL-7, IL-12, IL-15 and IL-18, and downregulatory ones, IL-1Rα, IL-10, α-MSH, CXCL10 and PGE2. T cells produce IFN-α, IL-17 and IL-4 that influence keratinocyte functions. Keratinocyte chemoattractant cytokines influence T-cell trafficking: IL-1, IL-8, CCL27, CCL5, CCL17, CXCL10, MIG, IP9, CCL20.

Figure 2.

Inflammasome basic structure consists of caspase-1, NLRs and ASC. The specific composition of an inflammasome is dependent on the activator, e.g., ATP, ROS, cathepsins, DAMPs, PAMPs, K⁺ efflux. The main action of the assembled inflammasome is to induce the conversion of pro-IL-1β in IL-1β. NLRs, nucleotide-binding oligomerization domain and leucine-rich repeat-containing receptors; ASC, apoptosis-associated speck-like protein; ROS, reactive oxygen species.

Figure 3.

Normal melanocytes subjected to various factors that induce genetic instability and inflammatory conditions can undergo malignant transformation to melanoma.