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 exper...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/14/2/171 |
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| author | Agata Mlynska Jolita Gibavičienė Otilija Kutanovaitė Linas Senkus Julija Mažeikaitė Ieva Kerševičiūtė Vygantė Maskoliūnaitė Neda Rupeikaitė Rasa Sabaliauskaitė Justina Gaiževska Karolina Suveizdė Jan Aleksander Kraśko Neringa Dobrovolskienė Emilija Paberalė Eglė Žymantaitė Vita Pašukonienė |
| author_facet | Agata Mlynska Jolita Gibavičienė Otilija Kutanovaitė Linas Senkus Julija Mažeikaitė Ieva Kerševičiūtė Vygantė Maskoliūnaitė Neda Rupeikaitė Rasa Sabaliauskaitė Justina Gaiževska Karolina Suveizdė Jan Aleksander Kraśko Neringa Dobrovolskienė Emilija Paberalė Eglė Žymantaitė Vita Pašukonienė |
| author_sort | Agata Mlynska |
| collection | DOAJ |
| description | 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: <i>CD2</i>, <i>CD53</i>, <i>IRF1</i>, and <i>CD8B</i>; and stroma-related: <i>COL5A2</i>, <i>TNFAIP6</i>, and <i>INHBA</i>) 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. |
| first_indexed | 2024-03-07T22:40:27Z |
| format | Article |
| id | doaj.art-3217e8fb3c2a402ca0ab8edb71b07c56 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-07T22:40:27Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-3217e8fb3c2a402ca0ab8edb71b07c562024-02-23T15:09:17ZengMDPI AGBiomolecules2218-273X2024-01-0114217110.3390/biom14020171Defining Melanoma Immune Biomarkers—Desert, Excluded, and Inflamed Subtypes—Using a Gene Expression Classifier Reflecting Intratumoral Immune Response and Stromal PatternsAgata Mlynska0Jolita Gibavičienė1Otilija Kutanovaitė2Linas Senkus3Julija Mažeikaitė4Ieva Kerševičiūtė5Vygantė Maskoliūnaitė6Neda Rupeikaitė7Rasa Sabaliauskaitė8Justina Gaiževska9Karolina Suveizdė10Jan Aleksander Kraśko11Neringa Dobrovolskienė12Emilija Paberalė13Eglė Žymantaitė14Vita Pašukonienė15National Cancer Institute, LT-08406 Vilnius, LithuaniaNational Cancer Institute, LT-08406 Vilnius, LithuaniaNational Cancer Institute, LT-08406 Vilnius, LithuaniaNational Cancer Institute, LT-08406 Vilnius, LithuaniaNational Cancer Institute, LT-08406 Vilnius, LithuaniaLife Sciences Center, Vilnius University, LT-01513 Vilnius, LithuaniaLife Sciences Center, Vilnius University, LT-01513 Vilnius, LithuaniaLife Sciences Center, Vilnius University, LT-01513 Vilnius, LithuaniaNational Cancer Institute, LT-08406 Vilnius, LithuaniaNational Cancer Institute, LT-08406 Vilnius, LithuaniaNational Cancer Institute, LT-08406 Vilnius, LithuaniaNational Cancer Institute, LT-08406 Vilnius, LithuaniaNational Cancer Institute, LT-08406 Vilnius, LithuaniaNational Cancer Institute, LT-08406 Vilnius, LithuaniaNational Cancer Institute, LT-08406 Vilnius, LithuaniaNational Cancer Institute, LT-08406 Vilnius, LithuaniaThe 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: <i>CD2</i>, <i>CD53</i>, <i>IRF1</i>, and <i>CD8B</i>; and stroma-related: <i>COL5A2</i>, <i>TNFAIP6</i>, and <i>INHBA</i>) 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.https://www.mdpi.com/2218-273X/14/2/171melanomatumor-infiltrating lymphocytesbiomarkersimmune subtypesdesertexcluded |
| spellingShingle | Agata Mlynska Jolita Gibavičienė Otilija Kutanovaitė Linas Senkus Julija Mažeikaitė Ieva Kerševičiūtė Vygantė Maskoliūnaitė Neda Rupeikaitė Rasa Sabaliauskaitė Justina Gaiževska Karolina Suveizdė Jan Aleksander Kraśko Neringa Dobrovolskienė Emilija Paberalė Eglė Žymantaitė Vita Pašukonienė Defining Melanoma Immune Biomarkers—Desert, Excluded, and Inflamed Subtypes—Using a Gene Expression Classifier Reflecting Intratumoral Immune Response and Stromal Patterns Biomolecules melanoma tumor-infiltrating lymphocytes biomarkers immune subtypes desert excluded |
| title | Defining Melanoma Immune Biomarkers—Desert, Excluded, and Inflamed Subtypes—Using a Gene Expression Classifier Reflecting Intratumoral Immune Response and Stromal Patterns |
| title_full | Defining Melanoma Immune Biomarkers—Desert, Excluded, and Inflamed Subtypes—Using a Gene Expression Classifier Reflecting Intratumoral Immune Response and Stromal Patterns |
| title_fullStr | Defining Melanoma Immune Biomarkers—Desert, Excluded, and Inflamed Subtypes—Using a Gene Expression Classifier Reflecting Intratumoral Immune Response and Stromal Patterns |
| title_full_unstemmed | Defining Melanoma Immune Biomarkers—Desert, Excluded, and Inflamed Subtypes—Using a Gene Expression Classifier Reflecting Intratumoral Immune Response and Stromal Patterns |
| title_short | Defining Melanoma Immune Biomarkers—Desert, Excluded, and Inflamed Subtypes—Using a Gene Expression Classifier Reflecting Intratumoral Immune Response and Stromal Patterns |
| title_sort | defining melanoma immune biomarkers desert excluded and inflamed subtypes using a gene expression classifier reflecting intratumoral immune response and stromal patterns |
| topic | melanoma tumor-infiltrating lymphocytes biomarkers immune subtypes desert excluded |
| url | https://www.mdpi.com/2218-273X/14/2/171 |
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