CXCL14 and mast cells: A potential interaction in melanoma

Summary: Abstract Body: This study investigates a role of CXCL14 and mast cells in melanoma. CXCL14, a non-ELR CXC chemokine, presents with conflicting pro-tumor and anti-tumor activity depending on tumor type and cellular source of CXCL14. Mast cells, tissue resident innate immune cells, are key modulators of the tumor microenvironment, exerting context specific tumor suppressive or progressive roles depending on tumor type. The role of CXCL14 and mast cells in melanoma remains unclear. By a bioinformatic analysis of TIMER2.0, we identified a positive correlation between CXCL14 and mast cell mRNA expression levels in clinical melanomas (p<0.05). By analyzing a public single-cell RNA sequencing dataset of 19 clinical melanomas, we identified that CXCL14 was mainly expressed in cancer associated fibroblasts. We co-stained CXCL14 (in situ hybridization) and various immune cells (immunohistochemistry) and found that the numbers of CXCL14-positive cells and mast cells were correlated both in the peritumoral area (p<0.01) and inside tumors in melanoma samples. Furthermore, we identified more CXCL14-positive cells in peritumoral areas of thinner (p<0.01) and low-grade (p<0.05) melanomas compared with those of thicker and high-grade. At this time, further studies are needed to understand why the numbers of CXCL14-positive cells and mast cells were correlated. Nonetheless, clarifying the role of CXCL14 and mast cells in melanoma pathogenesis would be useful to explore a new therapeutic target. Jenny Chung¹, Sanjay Lietzau², Mengyan Li², Akinori Kawakami², Kenji Kabashima² 1. The City College of New York CUNY School of Medicine, New York, NY, United States. 2. Dermatology, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan. Pigmentation, Melanoma, and Melanoma Immune Surveillance