Clinical and Immunologic Features of Germline Pathogenic Variant-Positive Patients with Melanoma
©2023 American Association for Cancer Research..
PURPOSE: Malignant melanoma represents the most lethal skin cancer with germline predispositions thought to comprise 10% to 15% of all melanoma cases. No studies to date examine the immunologic features that may differentiate survival differences between germline pathogenic variant (gPV)-positive patients with melanoma from gPV-negative patients with melanoma.
EXPERIMENTAL DESIGN: Adult patients with melanoma and clinical characteristics suggesting hereditary predisposition to cancer were prospectively recruited to undergo germline testing and flow cytometric analysis of peripheral immune suppressor cells.
RESULTS: In this cohort, gPV-positive patients (n = 72) had a significantly improved melanoma-specific survival (MSS) compared with gPV-negative patients (n = 411; HRadj, 0.32; 95% CI, 0.13-0.82; P = 0.01). These survival improvements among gPV-positive patients were most apparent among cutaneous melanoma subtypes (HRadj, 0.12; 95% CI, 0.016-0.86; P = 0.03) and numerically improved in later-stage (IIB-IV) patients (HRadj, 0.34; 95% CI, 0.10-1.11; P = 0.06). Further, gPV-positive patients had a significantly lower level of total circulating PMN-MDSC compared with gPV-negative patients (P = 0.01), which was most apparent in those diagnosed with later stages (IIB-IV) of melanoma (P = 0.009). Finally, a significant upregulation of inflammatory transcriptome signatures in later-stage gPV-positive patients (n = 21) was observed in comparison with gPV-negative patients (n = 173) in the cutaneous melanoma cohort (SKCM) of The Cancer Genome Atlas (TCGA).
CONCLUSIONS: gPV-positive patients with melanoma exhibit improved MSS in addition to reduced peripheral PMN-MDSC and an enhanced inflammatory microenvironment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Clinical cancer research : an official journal of the American Association for Cancer Research - 30(2024), 3 vom: 01. Feb., Seite 564-574 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shen, Alan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.02.2024 Date Revised 14.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1158/1078-0432.CCR-23-1964 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365234923 |
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| 245 | 1 | 0 | |a Clinical and Immunologic Features of Germline Pathogenic Variant-Positive Patients with Melanoma |
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| 500 | |a published: Print | ||
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| 520 | |a ©2023 American Association for Cancer Research. | ||
| 520 | |a PURPOSE: Malignant melanoma represents the most lethal skin cancer with germline predispositions thought to comprise 10% to 15% of all melanoma cases. No studies to date examine the immunologic features that may differentiate survival differences between germline pathogenic variant (gPV)-positive patients with melanoma from gPV-negative patients with melanoma | ||
| 520 | |a EXPERIMENTAL DESIGN: Adult patients with melanoma and clinical characteristics suggesting hereditary predisposition to cancer were prospectively recruited to undergo germline testing and flow cytometric analysis of peripheral immune suppressor cells | ||
| 520 | |a RESULTS: In this cohort, gPV-positive patients (n = 72) had a significantly improved melanoma-specific survival (MSS) compared with gPV-negative patients (n = 411; HRadj, 0.32; 95% CI, 0.13-0.82; P = 0.01). These survival improvements among gPV-positive patients were most apparent among cutaneous melanoma subtypes (HRadj, 0.12; 95% CI, 0.016-0.86; P = 0.03) and numerically improved in later-stage (IIB-IV) patients (HRadj, 0.34; 95% CI, 0.10-1.11; P = 0.06). Further, gPV-positive patients had a significantly lower level of total circulating PMN-MDSC compared with gPV-negative patients (P = 0.01), which was most apparent in those diagnosed with later stages (IIB-IV) of melanoma (P = 0.009). Finally, a significant upregulation of inflammatory transcriptome signatures in later-stage gPV-positive patients (n = 21) was observed in comparison with gPV-negative patients (n = 173) in the cutaneous melanoma cohort (SKCM) of The Cancer Genome Atlas (TCGA) | ||
| 520 | |a CONCLUSIONS: gPV-positive patients with melanoma exhibit improved MSS in addition to reduced peripheral PMN-MDSC and an enhanced inflammatory microenvironment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 700 | 1 | |a Arbesman, Michelle |e verfasserin |4 aut | |
| 700 | 1 | |a Lodha, Roshan |e verfasserin |4 aut | |
| 700 | 1 | |a Rayman, Patricia |e verfasserin |4 aut | |
| 700 | 1 | |a Bungo, Brandon |e verfasserin |4 aut | |
| 700 | 1 | |a Ni, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Timothy |e verfasserin |4 aut | |
| 700 | 1 | |a Gastman, Brian |e verfasserin |4 aut | |
| 700 | 1 | |a Ko, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Diaz-Montero, C Marcela |e verfasserin |4 aut | |
| 700 | 1 | |a Arbesman, Joshua |e verfasserin |4 aut | |
| 700 | 1 | |a Funchain, Pauline |e verfasserin |4 aut | |
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