B cells are associated with survival and immunotherapy response in sarcoma
By F. Petitprez, A. Reyniès, E. Keung, T. Chen, Cheng-Ming Sun, J. Calderaro, Y. Jeng, Li-Ping Hsiao, L. Lacroix, A. Bougoüin and 19 more. Nature, 2020
1,636 citations recorded by the source corpus.
Soft-tissue sarcomas represent a heterogeneous group of cancer, with more than 50 histological subtypes1,2. The clinical presentation of patients with different subtypes is often atypical, and responses to therapies such as immune checkpoint blockade vary widely3,4. To explain this clinical variability, here we study gene expression profiles in 608 tumours across subtypes of soft-tissue sarcoma. We establish an immune-based classification on the basis of the composition of the tumour microenvironment and identify five distinct phenotypes: immune-low (A and B), immune-high (D and E), and highly vascularized (C) groups. In situ analysis of an independent validation cohort shows that class E was characterized by the presence of tertiary lymphoid structures that contain T cells and follicular dendritic cells and are particularly rich in B cells. B cells are the strongest prognostic factor even in the context of high or low CD8+ T cells and cytotoxic contents. The class-E group demonstrated improved survival and a high response rate to PD1 blockade with pembrolizumab in a phase 2 clinical trial. Together, this work confirms the immune subtypes in patients with soft-tissue sarcoma, and unravels the potential of B-cell-rich tertiary lymphoid structures to guide clinical decision-making and treatments, which could have broader applications in other diseases. Immune profiling of the tumour microenvironment of soft-tissue sarcoma identifies a group of patients with high levels of B-cell infiltration and tertiary lymphoid structures that have improved survival and a high response rate to immune checkpoint blockade therapy.
Subfields: Oncology, Pathology and Forensic Medicine, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/7a53a5e84976a4c2a9e0d547af7b88422559a70f
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Citations in the corpus
- Tumor-infiltrating lymphocytes in the immunotherapy era (2020, background): “Furthermore, tumors enriched with B cell lineage signatures exhibited the highest response rate to ICB treatment.(241) Comparable results were found in tumor samples of metastatic melanoma patients.”
- Tertiary lymphoid structures in cancer (2022, background): “In addition, TFH cells have mostly been documented in TLSs in breast cancer (28, 71) and, more recently, in sarcoma (17).”
- Spatially organized multicellular immune hubs in human colorectal cancer (2021, background): “, 2016), contain germinal center B cells, and have been associated with high T cell activity, favorable prognosis, and effective response to immunotherapy (Cabrita et al., 2020; Coppola et al., 2011; Helmink et al., 2020; Petitprez et al., 2020; Sautès-Fridman et al., 2019).”
- Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front (2019, background): “The biological and clinical relevance of TLSs has been demonstrated not only in CRC but also in multiple other cancers (Binnewies et al., 2018; Cabrita et al., 2020; Di Caro et al., 2014; Dieu-Nosjean et al., 2016; Graham and Appelman, 1990; Helmink et al., 2020; Petitprez et al., 2020; Sautès-Fridm”
- Immune Cell Abundance and T-cell Receptor Landscapes Suggest New Patient Stratification Strategies in Head and Neck Squamous Cell Carcinoma (2023, unknown): “Several additional B-lineage markers previously shown to be associated with the presence of TLSs (28), such as CD79B, CD1D, and MS4A1 (CD20), were highest expressed in the cytotoxic and PC high groups (Fig.”