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Clonality, Antigen Recognition, and Suppression of CD8+ T Cells Differentially Affect Prognosis of Breast Cancer Subtypes.
Hammerl, Dora; Massink, Maarten P G; Smid, Marcel; van Deurzen, Carolien H M; Meijers-Heijboer, Hanne E J; Waisfisz, Quinten; Debets, Reno; Martens, John W M.
Afiliación
  • Hammerl D; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands. d.hammerl@erasmusmc.nl.
  • Massink MPG; Department of Genetics, University Medical Centre Utrecht, Utrecht, the Netherlands.
  • Smid M; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.
  • van Deurzen CHM; Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
  • Meijers-Heijboer HEJ; Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands.
  • Waisfisz Q; Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands.
  • Debets R; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Martens JWM; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.
Clin Cancer Res ; 26(2): 505-517, 2020 01 15.
Article en En | MEDLINE | ID: mdl-31649042
PURPOSE: In breast cancer, response rates to immune therapies are generally low and differ significantly across molecular subtypes, urging a better understanding of immunogenicity and immune evasion. EXPERIMENTAL DESIGN: We interrogated large gene-expression data sets including 867 node-negative, treatment-naïve breast cancer patients (microarray data) and 347 breast cancer patients (whole-genome sequencing and transcriptome data) according to parameters of T cells as well as immune microenvironment in relation to patient survival. RESULTS: We developed a 109-immune gene signature that captures abundance of CD8 tumor-infiltrating lymphocytes (TIL) and is prognostic in basal-like, her2, and luminal B breast cancer, but not in luminal A or normal-like breast cancer. Basal-like and her2 are characterized by highest CD8 TIL abundance, highest T-cell clonality, highest frequencies of memory T cells, and highest antigenicity, yet only the former shows highest expression level of immune and metabolic checkpoints and highest frequency of myeloid suppressor cells. Also, luminal B shows a high antigenicity and T-cell clonality, yet a low abundance of CD8 TILs. In contrast, luminal A and normal-like both show a low antigenicity, and notably, a low and high abundance of CD8 TILs, respectively, which associates with T-cell influx parameters, such as expression of adhesion molecules. CONCLUSIONS: Collectively, our data argue that not only CD8 T-cell presence itself, but rather T-cell clonality, T-cell subset distribution, coinhibition, and antigen presentation reflect occurrence of a CD8 T-cell response in breast cancer subtypes, which have been aborted by distinct T-cell-suppressive mechanisms, providing a rationale for subtype-specific combination immune therapies.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Biomarcadores de Tumor / Subgrupos de Linfocitos T / Células Clonales / Presentación de Antígeno / Linfocitos T CD8-positivos / Bases de Datos Genéticas Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2020 Tipo del documento: Article País de afiliación: Países Bajos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Biomarcadores de Tumor / Subgrupos de Linfocitos T / Células Clonales / Presentación de Antígeno / Linfocitos T CD8-positivos / Bases de Datos Genéticas Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2020 Tipo del documento: Article País de afiliación: Países Bajos