Clonality, Antigen Recognition, and Suppression of CD8 + T Cells Differentially Affect Prognosis of Breast Cancer Subtypes.

Autor:	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.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2020 Jan 15; Vol. 26 (2), pp. 505-517. Date of Electronic Publication: 2019 Oct 24.
DOI:	10.1158/1078-0432.CCR-19-0285
Abstrakt:	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. (©2019 American Association for Cancer Research.)
Databáze:	MEDLINE
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