Tumor microenvironment in non-melanoma skin cancer resistance to photodynamic therapy

Abstract

Non-melanoma skin cancer has recently seen an increase in prevalence, and it is estimated that this grow will continue in the coming years. In this sense, the importance of therapy effectiveness has increased, especially photodynamic therapy. Photodynamic therapy has attracted much attention as a minimally invasive, selective and repeatable approach for skin cancer treatment and prevention. Although its high efficiency, this strategy has also faced problems related to tumor resistance, where the tumor microenvironment has gained a well-deserved role in recent years. Tumor microenvironment denotes a wide variety of elements, such as cancer-associated fibroblasts, immune cells, endothelial cells or the extracellular matrix, where their interaction and the secretion of a wide diversity of cytokines. Therefore, the need of designing new strategies targeting elements of the tumor microenvironment to overcome the observed resistance has become evident. To this end, in this review we focus on the role of cancer-associated fibroblasts and tumor-associated macrophages in the resistance to photodynamic therapy. We are also exploring new approaches consisting in the combination of new and old drugs targeting these cells with photodynamic therapy to enhance treatment outcomes of non-melanoma skin cancer.

Topical Immunotherapy for Actinic Keratosis and Field Cancerization

“…Therefore, PDT can induce cellular death through apoptosis, necrosis, and autophagy [ 25 , 26 ]. PDT can also trigger an immune response by releasing damage-associated molecular patterns (DAMPs) from the dying cells [ 27 , 28 ]. DAMPs are molecules that signal tissue damage and activate innate and adaptive immunity.…”

“…DAMPs are molecules that signal tissue damage and activate innate and adaptive immunity. Some examples of DAMPs are calreticulin (CRT), ATP, and HMGB1 (high mobility group box 1 protein) [ 27 , 28 ]. These molecules can bind to specific receptors on antigen-presenting cells (APCs) and stimulate their maturation and migration to lymph nodes [ 25 , 27 , 28 ].…”

“…Some examples of DAMPs are calreticulin (CRT), ATP, and HMGB1 (high mobility group box 1 protein) [ 27 , 28 ]. These molecules can bind to specific receptors on antigen-presenting cells (APCs) and stimulate their maturation and migration to lymph nodes [ 25 , 27 , 28 ]. There, they present tumor antigens to T cells and initiate an anti-tumor immune response.…”

“…There, they present tumor antigens to T cells and initiate an anti-tumor immune response. PDT can also modulate the tumor microenvironment by affecting cancer-associated fibroblasts (CAFs) [ 27 ]. CAFs are fibroblasts that support tumor growth, invasion, and angiogenesis.…”

“…CAFs are fibroblasts that support tumor growth, invasion, and angiogenesis. PDT can reduce the number and activity of CAFs, thus inhibiting their pro-tumoral effects [ 27 ] ( Figure 1 ).…”