244 The sphingosine-1-phosphate-cathelicidin axis has a pivotal role in the development of cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (cSCC) is a common cancer, caused by mutagenesis from excess ultraviolet radiation (UVR) or other types of oxidative stress. These stressors also upregulate production key innate immune element, cathelicidin antimicrobial peptide (CAMP), via endoplasmic reticulum (ER) stress-initiated, sphingosine-1-phosphate (S1P) signaling. While CAMP has beneficial activities, it can be pro-inflammatory and pro-carcinogenic. We addressed whether/how S1P-induced leads to cSCC development. found that: 1) expression was markedly increased in cells patients’ skin; 2) inhibition S1P attenuated CAMP-stimulated growth; 3) exogenous stimulates growth, but not growth normal human keratinocytes; 4) blockade formyl receptor-like (FPRL) 1 protein (a receptor CAMP) activation as well the growth-promoting effects exogenously applied on cells, slowed invasion into an extracellular matrix-containing fibroblast substrate; 5) Foxp3+ regulatory T (Treg) (which diminish anti-tumor immunity) levels were skin. results suggest that relationship signaling overproduction crucial for Since Treg cancer microenvironment weaken anti-cancer immunity, we will address roles function cSCC.