Defining Melanoma Immune Biomarkers-Desert, Excluded, and Inflamed Subtypes-Using a Gene Expression Classifier Reflecting Intratumoral Immune Response and Stromal Patterns

The spatial distribution of tumor infiltrating lymphocytes (TILs) defines several histologically and clinically distinct immune subtypes-desert (no TILs), excluded (TILs in stroma), and inflamed (TILs in tumor parenchyma). To date, robust classification of immune subtypes still requires deeper experimental evidence across various cancer types. Here, we aimed to investigate, define, and validate the immune subtypes in melanoma by coupling transcriptional and histological assessments of the lymphocyte distribution in tumor parenchyma and stroma. We used the transcriptomic data from The Cancer Genome Atlas melanoma dataset to screen for the desert, excluded, and inflamed immune subtypes. We defined subtype-specific genes and used them to construct a subtype assignment algorithm. We validated the two-step algorithm in the qPCR data of real-world melanoma tumors with histologically defined immune subtypes. The accuracy of a classifier encompassing expression data of seven genes (immune response-related: CD2, CD53, IRF1, and CD8B; and stroma-related: COL5A2, TNFAIP6, and INHBA) in a validation cohort reached 79%. Our findings suggest that melanoma tumors can be classified into transcriptionally and histologically distinct desert, excluded, and inflamed subtypes. Gene expression-based algorithms can assist physicians and pathologists as biomarkers in the rapid assessment of a tumor immune microenvironment while serving as a tool for clinical decision making.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:14

Enthalten in:

Biomolecules - 14(2024), 2 vom: 31. Jan.

Sprache:

Englisch

Beteiligte Personen:

Mlynska, Agata [VerfasserIn]
Gibavičienė, Jolita [VerfasserIn]
Kutanovaitė, Otilija [VerfasserIn]
Senkus, Linas [VerfasserIn]
Mažeikaitė, Julija [VerfasserIn]
Kerševičiūtė, Ieva [VerfasserIn]
Maskoliūnaitė, Vygantė [VerfasserIn]
Rupeikaitė, Neda [VerfasserIn]
Sabaliauskaitė, Rasa [VerfasserIn]
Gaiževska, Justina [VerfasserIn]
Suveizdė, Karolina [VerfasserIn]
Kraśko, Jan Aleksander [VerfasserIn]
Dobrovolskienė, Neringa [VerfasserIn]
Paberalė, Emilija [VerfasserIn]
Žymantaitė, Eglė [VerfasserIn]
Pašukonienė, Vita [VerfasserIn]

Links:

Volltext

Themen:

Biomarkers
Biomarkers, Tumor
Classifier
Desert
Excluded
Gene expression
Immune subtypes
Inflamed
Journal Article
Melanoma
TCGA
Tumor microenvironment
Tumor-infiltrating lymphocytes

Anmerkungen:

Date Completed 26.02.2024

Date Revised 27.02.2024

published: Electronic

Citation Status MEDLINE

doi:

10.3390/biom14020171

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM368873897