Genetic Variants in Immune Related Genes as Predictors of Responsiveness to BCG Immunotherapy in Metastatic Melanoma Patients
Adjuvant immunotherapy in melanoma patients improves clinical outcomes. However, success is unpredictable due to inherited heterogeneity of immune responses. Inherent immune genes associated with single nucleotide polymorphisms (SNPs) may influence anti-tumor immune responses. We assessed the predic...
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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/1/91 |
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| author | Romela Irene Ramos Misa A. Shaw Leland Foshag Stacey L. Stern Negin Rahimzadeh David Elashoff Dave S. B. Hoon |
| author_facet | Romela Irene Ramos Misa A. Shaw Leland Foshag Stacey L. Stern Negin Rahimzadeh David Elashoff Dave S. B. Hoon |
| author_sort | Romela Irene Ramos |
| collection | DOAJ |
| description | Adjuvant immunotherapy in melanoma patients improves clinical outcomes. However, success is unpredictable due to inherited heterogeneity of immune responses. Inherent immune genes associated with single nucleotide polymorphisms (SNPs) may influence anti-tumor immune responses. We assessed the predictive ability of 26 immune-gene SNPs genomic panels for a clinical response to adjuvant BCG (Bacillus Calmette-Guérin) immunotherapy, using melanoma patient cohorts derived from three phase III multicenter clinical trials: AJCC (American Joint Committee on Cancer) stage IV patients given adjuvant BCG (<i>pilot cohort</i>; <i>n</i> = 92), AJCC stage III patients given adjuvant BCG (<i>verification cohort</i>; <i>n</i> = 269), and AJCC stage III patients that are sentinel lymph node (SLN) positive receiving no immunotherapy (<i>control cohort</i>; <i>n</i> = 80). The SNP panel analysis demonstrated that the responder patient group had an improved disease-free survival (DFS) (hazard ratio [HR] 1.84, 95% CI 1.09–3.13, <i>p</i> = 0.021) in the pilot cohort. In the verification cohort, an improved overall survival (OS) (HR 1.67, 95% CI 1.07–2.67, <i>p</i> = 0.025) was observed. No significant differences of SNPs were observed in DFS or OS in the control patient cohort. This study demonstrates that SNP immune genes can be utilized as a predictive tool for identifying melanoma patients that are inherently responsive to BCG and potentially other immunotherapies in the future. |
| first_indexed | 2024-03-10T13:39:51Z |
| format | Article |
| id | doaj.art-912acfdf3ac8418d807a84d9ddd77397 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T13:39:51Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-912acfdf3ac8418d807a84d9ddd773972023-11-21T03:10:24ZengMDPI AGCancers2072-66942020-12-011319110.3390/cancers13010091Genetic Variants in Immune Related Genes as Predictors of Responsiveness to BCG Immunotherapy in Metastatic Melanoma PatientsRomela Irene Ramos0Misa A. Shaw1Leland Foshag2Stacey L. Stern3Negin Rahimzadeh4David Elashoff5Dave S. B. Hoon6Department of Translational Molecular Medicine, John Wayne Cancer Institute, Santa Monica, CA 90404, USADepartment of Translational Molecular Medicine, John Wayne Cancer Institute, Santa Monica, CA 90404, USADivision of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, CA 90404, USADepartment of Biostatistics, John Wayne Cancer Institute, Santa Monica, CA 90404, USADepartment of Translational Molecular Medicine, John Wayne Cancer Institute, Santa Monica, CA 90404, USADepartment of Medicine Statistics Core, UCLA School of Medicine, Los Angeles, CA 90024, USADepartment of Translational Molecular Medicine, John Wayne Cancer Institute, Santa Monica, CA 90404, USAAdjuvant immunotherapy in melanoma patients improves clinical outcomes. However, success is unpredictable due to inherited heterogeneity of immune responses. Inherent immune genes associated with single nucleotide polymorphisms (SNPs) may influence anti-tumor immune responses. We assessed the predictive ability of 26 immune-gene SNPs genomic panels for a clinical response to adjuvant BCG (Bacillus Calmette-Guérin) immunotherapy, using melanoma patient cohorts derived from three phase III multicenter clinical trials: AJCC (American Joint Committee on Cancer) stage IV patients given adjuvant BCG (<i>pilot cohort</i>; <i>n</i> = 92), AJCC stage III patients given adjuvant BCG (<i>verification cohort</i>; <i>n</i> = 269), and AJCC stage III patients that are sentinel lymph node (SLN) positive receiving no immunotherapy (<i>control cohort</i>; <i>n</i> = 80). The SNP panel analysis demonstrated that the responder patient group had an improved disease-free survival (DFS) (hazard ratio [HR] 1.84, 95% CI 1.09–3.13, <i>p</i> = 0.021) in the pilot cohort. In the verification cohort, an improved overall survival (OS) (HR 1.67, 95% CI 1.07–2.67, <i>p</i> = 0.025) was observed. No significant differences of SNPs were observed in DFS or OS in the control patient cohort. This study demonstrates that SNP immune genes can be utilized as a predictive tool for identifying melanoma patients that are inherently responsive to BCG and potentially other immunotherapies in the future.https://www.mdpi.com/2072-6694/13/1/91SNPBacille Calmette–Guérinmetastatic melanomacancer immunologyadjuvant immunotherapyinnate immunity |
| spellingShingle | Romela Irene Ramos Misa A. Shaw Leland Foshag Stacey L. Stern Negin Rahimzadeh David Elashoff Dave S. B. Hoon Genetic Variants in Immune Related Genes as Predictors of Responsiveness to BCG Immunotherapy in Metastatic Melanoma Patients Cancers SNP Bacille Calmette–Guérin metastatic melanoma cancer immunology adjuvant immunotherapy innate immunity |
| title | Genetic Variants in Immune Related Genes as Predictors of Responsiveness to BCG Immunotherapy in Metastatic Melanoma Patients |
| title_full | Genetic Variants in Immune Related Genes as Predictors of Responsiveness to BCG Immunotherapy in Metastatic Melanoma Patients |
| title_fullStr | Genetic Variants in Immune Related Genes as Predictors of Responsiveness to BCG Immunotherapy in Metastatic Melanoma Patients |
| title_full_unstemmed | Genetic Variants in Immune Related Genes as Predictors of Responsiveness to BCG Immunotherapy in Metastatic Melanoma Patients |
| title_short | Genetic Variants in Immune Related Genes as Predictors of Responsiveness to BCG Immunotherapy in Metastatic Melanoma Patients |
| title_sort | genetic variants in immune related genes as predictors of responsiveness to bcg immunotherapy in metastatic melanoma patients |
| topic | SNP Bacille Calmette–Guérin metastatic melanoma cancer immunology adjuvant immunotherapy innate immunity |
| url | https://www.mdpi.com/2072-6694/13/1/91 |
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