Prognostic value of tertiary lymphoid structures in triple-negative breast cancer: integrated analysis with the tumor microenvironment and clinicopathological features
BackgroundIn triple-negative breast cancer (TNBC), the most immunogenic breast cancer type, tumor-infiltrating lymphocytes (TILs) are an independent prognostic factor. Tertiary lymphoid structures (TLS) are an important TILs source, but they are not integrated in the current prognostic criteria.Meth...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1507371/full |
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| author | Florence Boissière-Michot Marie-Christine Chateau Simon Thézenas Virginie Lafont Evelyne Crapez Evelyne Crapez Priyanka Sharma Angélique Bobrie Angélique Bobrie Pascal Roger Séverine Guiu Séverine Guiu William Jacot William Jacot William Jacot William Jacot |
| author_facet | Florence Boissière-Michot Marie-Christine Chateau Simon Thézenas Virginie Lafont Evelyne Crapez Evelyne Crapez Priyanka Sharma Angélique Bobrie Angélique Bobrie Pascal Roger Séverine Guiu Séverine Guiu William Jacot William Jacot William Jacot William Jacot |
| author_sort | Florence Boissière-Michot |
| collection | DOAJ |
| description | BackgroundIn triple-negative breast cancer (TNBC), the most immunogenic breast cancer type, tumor-infiltrating lymphocytes (TILs) are an independent prognostic factor. Tertiary lymphoid structures (TLS) are an important TILs source, but they are not integrated in the current prognostic criteria.MethodsIn this retrospective study, TLS were assessed in hematein-eosin-saffron-stained (HES) histological sections from 397 early, chemotherapy-naive TNBC samples after primary surgical resection. Their association with i) classical clinicopathological features, ii) TILs and CD3+, CD8+, CD20+ lymphoid populations, iii) CD68+, CD163+, CD11b+, CD66b+ myeloid populations, and iv) expression of the PD1/PD-L1 and PVR/TIGIT axis immune checkpoint components and their prognostic significance were evaluated.ResultsTLS were observed in 88.2% of samples, mainly in peritumoral areas (86.1%). Increased amount of peritumoral TLS (PT-TLS) was significantly associated with younger age (p<0.001), smaller tumor size and higher tumor grade (both, p<0.001), HER2null tumors (versus HER2low tumors, p<0.002), and non-lobular histological type (p<0.016). TNBC with higher PT-TLS abundance displayed more often a basal-like (p<0.001) and not molecular-apocrine phenotype (p<0.001). TLS abundance was associated with TILs and hot tumor inflammatory pattern (both, p<0.001). Remarkably, PT-TLS abundance was positively associated with the density of the analyzed lymphoid (CD3+, CD8+, CD20+) and myeloid (CD68+, CD163+, CD11b+) cell populations (all p<0.001), with the exception of CD66b+ cells, as well as with expression of the PD1/PD-L1 and TIGIT/PVR immune checkpoint markers. In univariate analysis, beside the classical clinicopathological factors (tumor size, node involvement and adjuvant chemotherapy), TILs, hot tumors and PT-TLS were significantly associated with clinical outcome. Moreover, the risk of relapse was inversely correlated with PT-TLS abundance (Kaplan-Meier analysis). In multivariate analysis, pathological stage, adjuvant chemotherapy and PT-TLS remained correlated with relapse-free survival.ConclusionOur results suggest that TLS are a frequent feature in early TNBC and that their presence, particularly at the tumor periphery, recapitulates the tumor immune microenvironment. In our series, their prognostic value outperformed that of TILs. Therefore, their easy quantification on routine HES sections and their integration into the factors classically analyzed by pathologists could improve the clinical management of TNBC, a breast cancer type whose prognosis remains too poor. |
| format | Article |
| id | doaj-art-51acdca94bd14828bff63a57737f642e |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-51acdca94bd14828bff63a57737f642e2025-08-20T02:33:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.15073711507371Prognostic value of tertiary lymphoid structures in triple-negative breast cancer: integrated analysis with the tumor microenvironment and clinicopathological featuresFlorence Boissière-Michot0Marie-Christine Chateau1Simon Thézenas2Virginie Lafont3Evelyne Crapez4Evelyne Crapez5Priyanka Sharma6Angélique Bobrie7Angélique Bobrie8Pascal Roger9Séverine Guiu10Séverine Guiu11William Jacot12William Jacot13William Jacot14William Jacot15Translational Research Unit, Montpellier Cancer Institute Val d’Aurelle, Montpellier, FranceTranslational Research Unit, Montpellier Cancer Institute Val d’Aurelle, Montpellier, FranceBiometry Department, Montpellier Cancer Institute Val d’Aurelle, Montpellier, FranceInstitut de Recherche en Cancérologie de Montpellier (IRCM), Inserm U1194, Montpellier, FranceTranslational Research Unit, Montpellier Cancer Institute Val d’Aurelle, Montpellier, FranceInstitut de Recherche en Cancérologie de Montpellier (IRCM), Inserm U1194, Montpellier, FranceInstitut de Recherche en Cancérologie de Montpellier (IRCM), Inserm U1194, Montpellier, FranceInstitut de Recherche en Cancérologie de Montpellier (IRCM), Inserm U1194, Montpellier, FranceDepartment of Medical Oncology, Montpellier Cancer Institute Val d’Aurelle, Montpellier, FrancePathology Department, Nîmes University Hospital, Nîmes, FranceInstitut de Recherche en Cancérologie de Montpellier (IRCM), Inserm U1194, Montpellier, FranceDepartment of Medical Oncology, Montpellier Cancer Institute Val d’Aurelle, Montpellier, FranceTranslational Research Unit, Montpellier Cancer Institute Val d’Aurelle, Montpellier, FranceInstitut de Recherche en Cancérologie de Montpellier (IRCM), Inserm U1194, Montpellier, FranceDepartment of Medical Oncology, Montpellier Cancer Institute Val d’Aurelle, Montpellier, FranceFaculty of Medicine, Montpellier University, Montpellier, FranceBackgroundIn triple-negative breast cancer (TNBC), the most immunogenic breast cancer type, tumor-infiltrating lymphocytes (TILs) are an independent prognostic factor. Tertiary lymphoid structures (TLS) are an important TILs source, but they are not integrated in the current prognostic criteria.MethodsIn this retrospective study, TLS were assessed in hematein-eosin-saffron-stained (HES) histological sections from 397 early, chemotherapy-naive TNBC samples after primary surgical resection. Their association with i) classical clinicopathological features, ii) TILs and CD3+, CD8+, CD20+ lymphoid populations, iii) CD68+, CD163+, CD11b+, CD66b+ myeloid populations, and iv) expression of the PD1/PD-L1 and PVR/TIGIT axis immune checkpoint components and their prognostic significance were evaluated.ResultsTLS were observed in 88.2% of samples, mainly in peritumoral areas (86.1%). Increased amount of peritumoral TLS (PT-TLS) was significantly associated with younger age (p<0.001), smaller tumor size and higher tumor grade (both, p<0.001), HER2null tumors (versus HER2low tumors, p<0.002), and non-lobular histological type (p<0.016). TNBC with higher PT-TLS abundance displayed more often a basal-like (p<0.001) and not molecular-apocrine phenotype (p<0.001). TLS abundance was associated with TILs and hot tumor inflammatory pattern (both, p<0.001). Remarkably, PT-TLS abundance was positively associated with the density of the analyzed lymphoid (CD3+, CD8+, CD20+) and myeloid (CD68+, CD163+, CD11b+) cell populations (all p<0.001), with the exception of CD66b+ cells, as well as with expression of the PD1/PD-L1 and TIGIT/PVR immune checkpoint markers. In univariate analysis, beside the classical clinicopathological factors (tumor size, node involvement and adjuvant chemotherapy), TILs, hot tumors and PT-TLS were significantly associated with clinical outcome. Moreover, the risk of relapse was inversely correlated with PT-TLS abundance (Kaplan-Meier analysis). In multivariate analysis, pathological stage, adjuvant chemotherapy and PT-TLS remained correlated with relapse-free survival.ConclusionOur results suggest that TLS are a frequent feature in early TNBC and that their presence, particularly at the tumor periphery, recapitulates the tumor immune microenvironment. In our series, their prognostic value outperformed that of TILs. Therefore, their easy quantification on routine HES sections and their integration into the factors classically analyzed by pathologists could improve the clinical management of TNBC, a breast cancer type whose prognosis remains too poor.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1507371/fulltertiary lymphoid structurestriple-negative breast cancertumor immune microenvironmentprognostic biomarkerpredictive biomarker |
| spellingShingle | Florence Boissière-Michot Marie-Christine Chateau Simon Thézenas Virginie Lafont Evelyne Crapez Evelyne Crapez Priyanka Sharma Angélique Bobrie Angélique Bobrie Pascal Roger Séverine Guiu Séverine Guiu William Jacot William Jacot William Jacot William Jacot Prognostic value of tertiary lymphoid structures in triple-negative breast cancer: integrated analysis with the tumor microenvironment and clinicopathological features Frontiers in Immunology tertiary lymphoid structures triple-negative breast cancer tumor immune microenvironment prognostic biomarker predictive biomarker |
| title | Prognostic value of tertiary lymphoid structures in triple-negative breast cancer: integrated analysis with the tumor microenvironment and clinicopathological features |
| title_full | Prognostic value of tertiary lymphoid structures in triple-negative breast cancer: integrated analysis with the tumor microenvironment and clinicopathological features |
| title_fullStr | Prognostic value of tertiary lymphoid structures in triple-negative breast cancer: integrated analysis with the tumor microenvironment and clinicopathological features |
| title_full_unstemmed | Prognostic value of tertiary lymphoid structures in triple-negative breast cancer: integrated analysis with the tumor microenvironment and clinicopathological features |
| title_short | Prognostic value of tertiary lymphoid structures in triple-negative breast cancer: integrated analysis with the tumor microenvironment and clinicopathological features |
| title_sort | prognostic value of tertiary lymphoid structures in triple negative breast cancer integrated analysis with the tumor microenvironment and clinicopathological features |
| topic | tertiary lymphoid structures triple-negative breast cancer tumor immune microenvironment prognostic biomarker predictive biomarker |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1507371/full |
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