Expression of lymphoid structure-associated cytokine/chemokine gene transcripts in tumor and protein in serum are prognostic of melanoma patient outcomes

• DOI: 10.3389/fimmu.2023.1171978
• Publication Date: 2023-06-24T10:12:47Z
• Authors: Lilit Karapetyan; Hassan M. AbuShukair; Aofei Li; Andrew Knight; Ayah Nedal Al Bzour; Ian P. MacFawn; Zachary J. Thompson; Ann Chen; Xi Yang; Rebekah Dadey; Arivarasan Karuna...; Danielle Vargas D...; Cindy Sander; Sheryl R. Kunning; Yana G. Najjar; Diwakar Davar; Jason J. Luke; William Gooding; Tullia C. Bruno; John M. Kirkwood; Walter J. Storkus
• Keywords: CXCL13

Background Proinflammatory chemokines/cytokines support development and maturation of tertiary lymphoid structures (TLS) within the tumor microenvironment (TME). In current study, we sought to investigate prognostic value TLS-associated (TLS-kines) expression levels in melanoma patients by performing serum protein tissue transcriptomic analyses, then correlate these data with clinicopathological TME characteristics. Methods Levels TLS-kines patients’ sera were quantitated using a custom Luminex Multiplex Assay. The Cancer Genomic Atlas cohort (TCGA-SKCM) Moffitt Melanoma used for analyses. Associations between target analytes survival outcomes, variables, correlations statistically analyzed. Results Serum 95 evaluated; 48 (50%) female, median age 63, IQR 51-70 years. APRIL/TNFSF13 positively correlated both CXCL10 CXCL13. multivariate high associated improved event-free after adjusting stage (HR = 0.64, 95% CI 0.43-0.95; p 0.03). High transcripts was significantly OS TCGA-SKCM 0.69, 0.52-0.93; 0.01) 0.51, CI: 0.32-0.82; 0.006). Further incorporation CXCL13 transcript 3-gene index revealed that APRIL/CXCL10/CXCL13 TCGA SKCM 0.42, 0.19-0.94; 0.035). differentially expressed genes linked infiltration diverse array proinflammatory immune cell types. Conclusion are outcomes. Patients exhibiting coordinate their tumors displayed superior OS. investigation TLS-kine profiles related clinical outcomes larger studies is warranted.