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Expression of lymphoid structure-associated cytokine/chemokine gene transcripts in tumor and protein in serum are prognostic of melanoma patient outcomes.
Karapetyan, Lilit; AbuShukair, Hassan M; Li, Aofei; Knight, Andrew; Al Bzour, Ayah Nedal; MacFawn, Ian P; Thompson, Zachary J; Chen, Ann; Yang, Xi; Dadey, Rebekah; Karunamurthy, Arivarasan; De Stefano, Danielle Vargas; Sander, Cindy; Kunning, Sheryl R; Najjar, Yana G; Davar, Diwakar; Luke, Jason J; Gooding, William; Bruno, Tullia C; Kirkwood, John M; Storkus, Walter J.
Afiliación
  • Karapetyan L; Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
  • AbuShukair HM; Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan.
  • Li A; Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, United States.
  • Knight A; Department of Medicine, Division of General Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, United States.
  • Al Bzour AN; Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan.
  • MacFawn IP; Department of Immunology, University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, Pittsburgh, PA, United States.
  • Thompson ZJ; Department of Bioinformatics and Biostatistics, The Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
  • Chen A; Department of Bioinformatics and Biostatistics, The Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
  • Yang X; Department of Medicine, Brigham and Women's Hospital and Dana Farber Cancer Institute, Boston, MA, United States.
  • Dadey R; Department of Immunology, University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, Pittsburgh, PA, United States.
  • Karunamurthy A; Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, United States.
  • De Stefano DV; Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, United States.
  • Sander C; Department of Immunology, University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, Pittsburgh, PA, United States.
  • Kunning SR; Department of Immunology, University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, Pittsburgh, PA, United States.
  • Najjar YG; Department of Medicine, Hillman Cancer Center, Division of Hematology/Oncology; University of Pittsburgh Medical Center, Pittsburgh, PA, United States.
  • Davar D; Department of Medicine, Hillman Cancer Center, Division of Hematology/Oncology; University of Pittsburgh Medical Center, Pittsburgh, PA, United States.
  • Luke JJ; Department of Medicine, Hillman Cancer Center, Division of Hematology/Oncology; University of Pittsburgh Medical Center, Pittsburgh, PA, United States.
  • Gooding W; Hillman Cancer Center Biostatistics Facility, University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, United States.
  • Bruno TC; Tumor Microenvironment Center, University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, Pittsburgh, PA, United States.
  • Kirkwood JM; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
  • Storkus WJ; Department of Medicine, Hillman Cancer Center, Division of Hematology/Oncology; University of Pittsburgh Medical Center, Pittsburgh, PA, United States.
Front Immunol ; 14: 1171978, 2023.
Article en En | MEDLINE | ID: mdl-37435077
Background: Proinflammatory chemokines/cytokines support development and maturation of tertiary lymphoid structures (TLS) within the tumor microenvironment (TME). In the current study, we sought to investigate the prognostic value of TLS-associated chemokines/cytokines (TLS-kines) expression levels in melanoma patients by performing serum protein and tissue transcriptomic analyses, and to then correlate these data with patients clinicopathological and TME characteristics. Methods: Levels of TLS-kines in patients' sera were quantitated using a custom Luminex Multiplex Assay. The Cancer Genomic Atlas melanoma cohort (TCGA-SKCM) and a Moffitt Melanoma cohort were used for tissue transcriptomic analyses. Associations between target analytes and survival outcomes, clinicopathological variables, and correlations between TLS-kines were statistically analyzed. Results: Serum of 95 patients with melanoma were evaluated; 48 (50%) female, median age of 63, IQR 51-70 years. Serum levels of APRIL/TNFSF13 were positively correlated with levels of both CXCL10 and CXCL13. In multivariate analyses, high levels of serum APRIL/TNFSF13 were associated with improved event-free survival after adjusting for age and stage (HR = 0.64, 95% CI 0.43-0.95; p = 0.03). High expression of APRIL/TNFSF13 tumor transcripts was significantly associated with improved OS in TCGA-SKCM (HR = 0.69, 95% CI 0.52-0.93; p = 0.01) and in Moffitt Melanoma patients (HR = 0.51, 95% CI: 0.32-0.82; p = 0.006). Further incorporation of CXCL13 and CXCL10 tumor transcript levels in a 3-gene index revealed that high APRIL/CXCL10/CXCL13 expression was associated with improved OS in the TCGA SKCM cohort (HR = 0.42, 95% CI 0.19-0.94; p = 0.035). Melanoma differentially expressed genes positively associated with high APRIL/CXCL10/CXCL13 tumor expression were linked to tumor infiltration by a diverse array of proinflammatory immune cell types. Conclusion: Serum protein and tumor transcript levels of APRIL/TNFSF13 are associated with improved survival outcomes. Patients exhibiting high coordinate expression of APRIL/CXCL10/CXCL13 transcripts in their tumors displayed superior OS. Further investigation of TLS-kine expression profiles related to clinical outcomes in larger cohort studies is warranted.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Melanoma Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Front Immunol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Melanoma Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Front Immunol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza