Interferon-gamma signature as prognostic and predictive marker in macroscopic stage III melanoma
Background A substantial proportion of patients with macroscopic stage III melanoma do not benefit sufficiently from adjuvant anti-PD-1 therapy, as they either recur despite therapy or would never have recurred. To better inform adjuvant treatment selection, we have performed translational analyses...
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BMJ Publishing Group
2024-04-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/4/e008125.full |
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| author | Annegien Broeks Michel W J M Wouters Georgina V Long Richard A Scolyer Christian U Blank Judith M Versluis Karijn P M Suijkerbuijk Petros Dimitriadis Joyce Sanders James S Wilmott Alexander Maxwell Menzies Yvonne M Schrage Stephanie A Blankenstein Robert Elens Willeke A M Blokx Winan van Houdt Alexander C J van Akkooi |
| author_facet | Annegien Broeks Michel W J M Wouters Georgina V Long Richard A Scolyer Christian U Blank Judith M Versluis Karijn P M Suijkerbuijk Petros Dimitriadis Joyce Sanders James S Wilmott Alexander Maxwell Menzies Yvonne M Schrage Stephanie A Blankenstein Robert Elens Willeke A M Blokx Winan van Houdt Alexander C J van Akkooi |
| author_sort | Annegien Broeks |
| collection | DOAJ |
| description | Background A substantial proportion of patients with macroscopic stage III melanoma do not benefit sufficiently from adjuvant anti-PD-1 therapy, as they either recur despite therapy or would never have recurred. To better inform adjuvant treatment selection, we have performed translational analyses to identify prognostic and predictive biomarkers.Patients and methods Two cohorts of patients with macroscopic stage III melanoma from an ongoing biobank study were included. Clinical data were compared between an observation cohort (cohort 1) and an adjuvant intention cohort (cohort 2). RNA sequencing for translational analyses was performed and treatment subgroups (cohort 1A and cohort 2A) were compared for possible biomarkers, using a cut-off based on the treatment-naïve patients. In addition, two validation cohorts (Melanoma Institute Australia (MIA) and University Medical Centre Utrecht (UMCU)) were obtained.Results After a median follow-up of 26 months of the 98 patients in our discovery set, median recurrence-free survival (RFS) was significantly longer for the adjuvant intention cohort (cohort 2, n=49) versus the observation cohort (cohort 1, n=49). Median overall survival was not reached for either cohort, nor significantly different. In observation cohort 1A (n=24), RFS was significantly longer for patients with high interferon-gamma (IFNγ) score (p=0.002); for adjuvant patients of cohort 2A (n=24), a similar trend was observed (p=0.086). Patients with high B cell score had a longer RFS in cohort 1A, but no difference was seen in cohort 2A. The B cell score based on RNA correlated with CD20+ cells in tumor area but was not independent from the IFNγ score. In the MIA validation cohort (n=44), longer RFS was observed for patients with high IFNγ score compared with low IFNγ score (p=0.046), no difference in RFS was observed according to the B cell score. In both the observation (n=11) and the adjuvant (n=11) UMCU validation cohorts, no difference in RFS was seen for IFNγ and B cell.Conclusions IFNγ has shown to be a prognostic marker in both patients who were and were not treated with adjuvant therapy. B cell score was prognostic but did not improve accuracy over IFNγ. Our study confirmed RFS benefit of adjuvant anti-PD-1 for patients with macroscopic stage III melanoma. |
| format | Article |
| id | doaj-art-e0b90991b4304091afe1ffd233fc064c |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-04-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-e0b90991b4304091afe1ffd233fc064c2025-08-20T02:14:49ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-04-0112410.1136/jitc-2023-008125Interferon-gamma signature as prognostic and predictive marker in macroscopic stage III melanomaAnnegien Broeks0Michel W J M Wouters1Georgina V Long2Richard A Scolyer3Christian U Blank4Judith M Versluis5Karijn P M Suijkerbuijk6Petros Dimitriadis7Joyce Sanders8James S Wilmott9Alexander Maxwell Menzies10Yvonne M Schrage11Stephanie A Blankenstein12Robert Elens13Willeke A M Blokx14Winan van Houdt15Alexander C J van Akkooi167 Core Facility Molecular Pathology and Biobanking, Netherlands Cancer Institute, Amsterdam, The Netherlands2 Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands4 Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia12 Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, NSW, Australia1 Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands1 Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands13 Department of Medical Oncology, UMC Utrecht, Utrecht, The Netherlands3 Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands11 Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands5 Melanoma Institute Australia, Sydney, New South Wales, Australia4 Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia2 Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands2 Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands7 Core Facility Molecular Pathology and Biobanking, Netherlands Cancer Institute, Amsterdam, The Netherlands8 Department of Pathology, UMC Utrecht, Utrecht, The Netherlands31 Department of Surgery, Netherlands Cancer Institute, Amsterdam, Netherlands2 Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The NetherlandsBackground A substantial proportion of patients with macroscopic stage III melanoma do not benefit sufficiently from adjuvant anti-PD-1 therapy, as they either recur despite therapy or would never have recurred. To better inform adjuvant treatment selection, we have performed translational analyses to identify prognostic and predictive biomarkers.Patients and methods Two cohorts of patients with macroscopic stage III melanoma from an ongoing biobank study were included. Clinical data were compared between an observation cohort (cohort 1) and an adjuvant intention cohort (cohort 2). RNA sequencing for translational analyses was performed and treatment subgroups (cohort 1A and cohort 2A) were compared for possible biomarkers, using a cut-off based on the treatment-naïve patients. In addition, two validation cohorts (Melanoma Institute Australia (MIA) and University Medical Centre Utrecht (UMCU)) were obtained.Results After a median follow-up of 26 months of the 98 patients in our discovery set, median recurrence-free survival (RFS) was significantly longer for the adjuvant intention cohort (cohort 2, n=49) versus the observation cohort (cohort 1, n=49). Median overall survival was not reached for either cohort, nor significantly different. In observation cohort 1A (n=24), RFS was significantly longer for patients with high interferon-gamma (IFNγ) score (p=0.002); for adjuvant patients of cohort 2A (n=24), a similar trend was observed (p=0.086). Patients with high B cell score had a longer RFS in cohort 1A, but no difference was seen in cohort 2A. The B cell score based on RNA correlated with CD20+ cells in tumor area but was not independent from the IFNγ score. In the MIA validation cohort (n=44), longer RFS was observed for patients with high IFNγ score compared with low IFNγ score (p=0.046), no difference in RFS was observed according to the B cell score. In both the observation (n=11) and the adjuvant (n=11) UMCU validation cohorts, no difference in RFS was seen for IFNγ and B cell.Conclusions IFNγ has shown to be a prognostic marker in both patients who were and were not treated with adjuvant therapy. B cell score was prognostic but did not improve accuracy over IFNγ. Our study confirmed RFS benefit of adjuvant anti-PD-1 for patients with macroscopic stage III melanoma.https://jitc.bmj.com/content/12/4/e008125.full |
| spellingShingle | Annegien Broeks Michel W J M Wouters Georgina V Long Richard A Scolyer Christian U Blank Judith M Versluis Karijn P M Suijkerbuijk Petros Dimitriadis Joyce Sanders James S Wilmott Alexander Maxwell Menzies Yvonne M Schrage Stephanie A Blankenstein Robert Elens Willeke A M Blokx Winan van Houdt Alexander C J van Akkooi Interferon-gamma signature as prognostic and predictive marker in macroscopic stage III melanoma Journal for ImmunoTherapy of Cancer |
| title | Interferon-gamma signature as prognostic and predictive marker in macroscopic stage III melanoma |
| title_full | Interferon-gamma signature as prognostic and predictive marker in macroscopic stage III melanoma |
| title_fullStr | Interferon-gamma signature as prognostic and predictive marker in macroscopic stage III melanoma |
| title_full_unstemmed | Interferon-gamma signature as prognostic and predictive marker in macroscopic stage III melanoma |
| title_short | Interferon-gamma signature as prognostic and predictive marker in macroscopic stage III melanoma |
| title_sort | interferon gamma signature as prognostic and predictive marker in macroscopic stage iii melanoma |
| url | https://jitc.bmj.com/content/12/4/e008125.full |
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