Histological Subtypes Drive Distinct Prognostic Immune Signatures in Classical Hodgkin Lymphoma
Despite the success of standard front-line chemotherapy, 20% of classical Hodgkin lymphoma (cHL) patients still relapse or have refractory disease (r/r), and a subset of them die due to disease progression. There is a critical lack of predictive factors for early identification of those r/r patients...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/19/4893 |
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| author | Claire Lamaison Juliette Ferrant Pauline Gravelle Alexandra Traverse-Glehen Hervé Ghesquières Marie Tosolini Cédric Rossi Loic Ysebaert Pierre Brousset Camille Laurent Charlotte Syrykh |
| author_facet | Claire Lamaison Juliette Ferrant Pauline Gravelle Alexandra Traverse-Glehen Hervé Ghesquières Marie Tosolini Cédric Rossi Loic Ysebaert Pierre Brousset Camille Laurent Charlotte Syrykh |
| author_sort | Claire Lamaison |
| collection | DOAJ |
| description | Despite the success of standard front-line chemotherapy, 20% of classical Hodgkin lymphoma (cHL) patients still relapse or have refractory disease (r/r), and a subset of them die due to disease progression. There is a critical lack of predictive factors for early identification of those r/r patients who may benefit from new therapeutic strategies. This study aimed to evaluate the dynamic expression of 586 immune-related genes in a cohort of 42 cHL patients including 30 r/r cHL after first-line chemotherapy. Gene expression profiling (GEP) using NanoString technology identified a 19-gene immune signature at diagnosis predictive of cHL relapse, but dependent on histological subtypes. Genes related to tumor survival were found upregulated while genes related to B-lineage were downregulated at diagnosis in r/r nodular sclerosis cHL. In contrast to the mixed-cellularity subtype, comparative GEP analyses between paired diagnosis/relapse biopsies of nodular sclerosis cHL showed 118 differentially expressed genes, supporting an immune contexture switch at relapse with upregulation of immunosuppressive cytokines, such as <i>LGALS1</i> and <i>TGFB1</i>, and downregulation of the T-cell co-stimulatory receptor <i>ICOS</i>. These results indicate that the predictive value of immune signature in cHL is strongly influenced by histological subtype which should be considered when assessing new immunotherapy target strategies. |
| first_indexed | 2024-03-09T21:55:43Z |
| format | Article |
| id | doaj.art-65127609017e42d28a5ab706a1b2a84f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T21:55:43Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-65127609017e42d28a5ab706a1b2a84f2023-11-23T19:58:22ZengMDPI AGCancers2072-66942022-10-011419489310.3390/cancers14194893Histological Subtypes Drive Distinct Prognostic Immune Signatures in Classical Hodgkin LymphomaClaire Lamaison0Juliette Ferrant1Pauline Gravelle2Alexandra Traverse-Glehen3Hervé Ghesquières4Marie Tosolini5Cédric Rossi6Loic Ysebaert7Pierre Brousset8Camille Laurent9Charlotte Syrykh10Centre Hospitalier Universitaire de Rennes, Pôle Biologie, 35033 Rennes, FranceCentre Hospitalier Universitaire de Rennes, Pôle Biologie, 35033 Rennes, FranceService d’Anatomopathologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse-Oncopole, 31059 Toulouse, FranceService d’Anatomopathologie, Centre Hospitalier Universitaire de Lyon-Sud, 69495 Lyon, FranceService d’Hématologie, Centre Hospitalier Universitaire de Lyon-Sud, Université Claude Bernard Lyon-1, Pierre-Bénite, 69495 Lyon, FranceCentre de Recherches en Cancérologie de Toulouse, INSERM, U1037, 31037 Toulouse, FranceService d’Hématologie, Centre Hospitalier Universitaire Dijon, Hôpital François Mitterrand, 21000 Dijon, FranceCentre de Recherches en Cancérologie de Toulouse, INSERM, U1037, 31037 Toulouse, FranceService d’Anatomopathologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse-Oncopole, 31059 Toulouse, FranceService d’Anatomopathologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse-Oncopole, 31059 Toulouse, FranceService d’Anatomopathologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse-Oncopole, 31059 Toulouse, FranceDespite the success of standard front-line chemotherapy, 20% of classical Hodgkin lymphoma (cHL) patients still relapse or have refractory disease (r/r), and a subset of them die due to disease progression. There is a critical lack of predictive factors for early identification of those r/r patients who may benefit from new therapeutic strategies. This study aimed to evaluate the dynamic expression of 586 immune-related genes in a cohort of 42 cHL patients including 30 r/r cHL after first-line chemotherapy. Gene expression profiling (GEP) using NanoString technology identified a 19-gene immune signature at diagnosis predictive of cHL relapse, but dependent on histological subtypes. Genes related to tumor survival were found upregulated while genes related to B-lineage were downregulated at diagnosis in r/r nodular sclerosis cHL. In contrast to the mixed-cellularity subtype, comparative GEP analyses between paired diagnosis/relapse biopsies of nodular sclerosis cHL showed 118 differentially expressed genes, supporting an immune contexture switch at relapse with upregulation of immunosuppressive cytokines, such as <i>LGALS1</i> and <i>TGFB1</i>, and downregulation of the T-cell co-stimulatory receptor <i>ICOS</i>. These results indicate that the predictive value of immune signature in cHL is strongly influenced by histological subtype which should be considered when assessing new immunotherapy target strategies.https://www.mdpi.com/2072-6694/14/19/4893Hodgkin lymphomaimmune prognosis signaturehistological subtypesgene expression profiling |
| spellingShingle | Claire Lamaison Juliette Ferrant Pauline Gravelle Alexandra Traverse-Glehen Hervé Ghesquières Marie Tosolini Cédric Rossi Loic Ysebaert Pierre Brousset Camille Laurent Charlotte Syrykh Histological Subtypes Drive Distinct Prognostic Immune Signatures in Classical Hodgkin Lymphoma Cancers Hodgkin lymphoma immune prognosis signature histological subtypes gene expression profiling |
| title | Histological Subtypes Drive Distinct Prognostic Immune Signatures in Classical Hodgkin Lymphoma |
| title_full | Histological Subtypes Drive Distinct Prognostic Immune Signatures in Classical Hodgkin Lymphoma |
| title_fullStr | Histological Subtypes Drive Distinct Prognostic Immune Signatures in Classical Hodgkin Lymphoma |
| title_full_unstemmed | Histological Subtypes Drive Distinct Prognostic Immune Signatures in Classical Hodgkin Lymphoma |
| title_short | Histological Subtypes Drive Distinct Prognostic Immune Signatures in Classical Hodgkin Lymphoma |
| title_sort | histological subtypes drive distinct prognostic immune signatures in classical hodgkin lymphoma |
| topic | Hodgkin lymphoma immune prognosis signature histological subtypes gene expression profiling |
| url | https://www.mdpi.com/2072-6694/14/19/4893 |
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