Background: Active recruitment of inflammatory cells into tumors may be vital for antitumor immunity in cutaneous squamous cell carcinoma (cSCC) after photodynamic therapy. Chemokines play important roles in inflammatory cell recruitment. Moreover, C-X-C motif chemokine ligand 13 (CXCL13) is thought to be a pivotal chemokine involved in inflammatory response and antitumor effect. Here, we examined the roles of CXCL13 in the response of cSCC to ALA-PDT.
Methods: Microarray analysis was used to select the chemokines involved in cSCC treated with ALA-PDT. The expression and transcriptional activity of CXCL13 were assessed by immunohistochemistry and quantitative real-time polymerase chain reaction. Western blotting was used to detect C-X-C motif chemokine receptor 5 (CXCR5) expression. The role of CXCL13 in ALA-PDT efficacy was assessed in vivo.
Results: Microarray analysis of total 63 chemokines and their receptors showed that the expression of 21 chemokines and 13 receptors were up-regulated in cSCC after ALA-PDT; in particular, CXCL13 was significantly upregulated. Immunohistochemistry showed that cancer-associated fibroblasts (CAFs) may be the main source of CXCL13 upregulation in the cSCC microenvironment after ALA-PDT. The efficacy of ALA-PDT in the treatment of cSCC was significantly reduced after CXCL13 inhibition.
Conclusion: CXCL13 plays important roles in the antitumor effect of ALA-PDT for cSCC and may originate mainly from CAFs in the cSCC microenvironment.
Keywords: 5-Aminolevulinic acid-photodynamic therapy; Antitumor immunity; C-X-C motif chemokine ligand 13; Cutaneous squamous cell carcinoma.
Copyright © 2019. Published by Elsevier B.V.