Identification of high-risk patients with a seven-biomarker prognostic signature for adjuvant treatment trial recruitment in American Joint Committee on Cancer v8 stage I–IIA cutaneous melanoma

The role of tissue-resident memory T cells as mediators for response and toxicity in immunotherapy-treated melanoma—two sides of the same coin?

“…We are still missing reliable and mechanistically motivated tissuebased biomarkers that guide ICI at different stages of melanoma therapy. The tumor-intrinsic risk of recurrence in stage I-III melanomas can be classified with an immunohistochemical signature consisting of Bax, Bcl-X, PTEN, COX-2, b-catenin, MTAP, and CD20 (58)(59)(60). This signature, however, does not contain markers relevant to T cells which are the main target of ICI.…”

Analytical Validation of an Immunohistochemical 7-Biomarker Prognostic Assay (immunoprint®) for Early-Stage Cutaneous Melanoma in Archival Tissue of Patients with AJCC v8 T2–T3 Disease

“…Notably, in a large (N = 439) study by Meyer et al [13], 7-marker signature high-risk classification could identify stage I-IIA patients with a 7.5-year (MSS) resembling 10-year MSS in stage IIB or stage IIC patients in two cohorts studied by Garbe et al [4] or in the AJCC v8 cohort [15]. In the Meyer et al study [13], 7.5-year MSS was 74.3% (95% Figure 1. 7-marker signature assay (immunoprint ® ) workflow.…”

“…Notably, in a large (N = 439) study by Meyer et al [13], 7-marker signature high-risk classification could identify stage I-IIA patients with a 7.5-year (MSS) resembling 10-year MSS in stage IIB or stage IIC patients in two cohorts studied by Garbe et al [4] or in the AJCC v8 cohort [15]. In the Meyer et al study [13], 7.5-year MSS was 74.3% (95% confidence interval [CI] 62.1-88.8%) in stage IA-IIA patients classified as high-risk by the 7-marker signature assay, and 71.8% (95% CI 58.6-88.1%) in stage IB-IIA subgroup members with the high-risk classification. In comparison, 10-year MSS was 72.0-79.9% in stage IIB patients and 57.6-64.7% in stage IIC patients in the Garbe et al cohorts [4], and 82% and 75%, respectively, in such patients in the AJCC v8 cohort [15].…”

“…The 7-marker signature assay dichotomizes patients into a high-risk classification or a low-risk classification (Figure 1) regarding disease-free survival/RFS, distant metastasisfree survival, melanoma-specific survival (MSS), and/or overall survival [12][13][14]. It does so by generating a total score based on the presence in primary melanoma tissue of five "risk" markers (Bax, Bcl-X, COX-2, PTEN, and CD20-positive B-lymphocytes) and two "protective" markers (loss of MTAP and of ß-catenin) [12].…”

“…To date, clinical validation of 7-marker signature assay risk data as a significant independent predictor of melanoma survival outcomes has been reported in a total of 762 patients from three independent cohorts [12][13][14]. Such validation has taken place both retrospectively [12,14] and using prospectively-collected specimens [13], in the presence [14] and absence [12] of sentinel lymph node staging, and applying both tissue microarrays [12] and the whole-tissue melanoma sections [13,14] more typically encountered in clinical routine.…”