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] |
---|
Links: |
---|
Themen: |
Biomarkers |
---|
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 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM368873897 | ||
003 | DE-627 | ||
005 | 20240229164629.0 | ||
007 | cr uuu---uuuuu | ||
008 | 240229s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.3390/biom14020171 |2 doi | |
028 | 5 | 2 | |a pubmed24n1309.xml |
035 | |a (DE-627)NLM368873897 | ||
035 | |a (NLM)38397409 | ||
035 | |a (PII)171 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Mlynska, Agata |e verfasserin |4 aut | |
245 | 1 | 0 | |a Defining Melanoma Immune Biomarkers-Desert, Excluded, and Inflamed Subtypes-Using a Gene Expression Classifier Reflecting Intratumoral Immune Response and Stromal Patterns |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 26.02.2024 | ||
500 | |a Date Revised 27.02.2024 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a TCGA | |
650 | 4 | |a biomarkers | |
650 | 4 | |a classifier | |
650 | 4 | |a desert | |
650 | 4 | |a excluded | |
650 | 4 | |a gene expression | |
650 | 4 | |a immune subtypes | |
650 | 4 | |a inflamed | |
650 | 4 | |a melanoma | |
650 | 4 | |a tumor microenvironment | |
650 | 4 | |a tumor-infiltrating lymphocytes | |
650 | 7 | |a Biomarkers |2 NLM | |
650 | 7 | |a Biomarkers, Tumor |2 NLM | |
700 | 1 | |a Gibavičienė, Jolita |e verfasserin |4 aut | |
700 | 1 | |a Kutanovaitė, Otilija |e verfasserin |4 aut | |
700 | 1 | |a Senkus, Linas |e verfasserin |4 aut | |
700 | 1 | |a Mažeikaitė, Julija |e verfasserin |4 aut | |
700 | 1 | |a Kerševičiūtė, Ieva |e verfasserin |4 aut | |
700 | 1 | |a Maskoliūnaitė, Vygantė |e verfasserin |4 aut | |
700 | 1 | |a Rupeikaitė, Neda |e verfasserin |4 aut | |
700 | 1 | |a Sabaliauskaitė, Rasa |e verfasserin |4 aut | |
700 | 1 | |a Gaiževska, Justina |e verfasserin |4 aut | |
700 | 1 | |a Suveizdė, Karolina |e verfasserin |4 aut | |
700 | 1 | |a Kraśko, Jan Aleksander |e verfasserin |4 aut | |
700 | 1 | |a Dobrovolskienė, Neringa |e verfasserin |4 aut | |
700 | 1 | |a Paberalė, Emilija |e verfasserin |4 aut | |
700 | 1 | |a Žymantaitė, Eglė |e verfasserin |4 aut | |
700 | 1 | |a Pašukonienė, Vita |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Biomolecules |d 2011 |g 14(2024), 2 vom: 31. Jan. |w (DE-627)NLM228347106 |x 2218-273X |7 nnns |
773 | 1 | 8 | |g volume:14 |g year:2024 |g number:2 |g day:31 |g month:01 |
856 | 4 | 0 | |u http://dx.doi.org/10.3390/biom14020171 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 14 |j 2024 |e 2 |b 31 |c 01 |