B cells sustain inflammation and predict response to immune checkpoint blockade in human melanoma

Griss, Johannes; Bauer, Wolfgang; Wagner, Christine; Simón, Martín; Chen, Minyi; Grabmeier‐Pfistershammer, Katharina; Maurer‐Granofszky, Margarita; Roka, Florian; Penz, Thomas; Bock, Christoph; Zhang, Gao; Herlyn, Meenhard; Glatz, Katharina; Läubli, Heinz; Mertz, Kirsten D.; Petzelbauer, Peter; Wiesner, Thomas; Hartl, Markus; Pickl, Winfried F.; Somasundaram, Rajasekharan; Schmitz, Peter; Wagner, Stephan N.

doi:10.1038/s41467-019-12160-2

Cited by 284 publications

(214 citation statements)

References 93 publications

(124 reference statements)

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“…As highlighted in our example data and previous studies, such differences are to be expected 17,23 . We deliberately developed a system that can highlight such differences that researchers can interactively investigate with the Reactome pathway browser.…”

Section: Discussionsupporting

confidence: 77%

“…64 of these pathways showed a differential regulation in one of the datasets compared to melanoma. We previously showed in vitro that NF-kappaB activation was significantly up-regulated in B cells after stimulation with melanoma conditioned medium 17 . Lung adenocarcinoma samples were the only ones that showed a significant down-regulation of the "Activation of NF-kappaB in B cells" pathway (FDR = 0.08).…”

Section: Lung Adenocarcinomamentioning

confidence: 99%

“…We were among the first to show that B cells play a crucial role in anti-tumour immunity in human melanoma 17 . In vitro , B cells differentiate towards a tumor-induced, plasmablast-like (TIPB) phenotype in the presence of melanoma cells.…”

Section: Lung Adenocarcinomamentioning

confidence: 99%

“…Specific subtypes of B cells seem to be primarily responsible for the B cell triggered anti-tumour response 17,[25][26][27] . We therefore assessed whether the observed difference in NFϰB activation is B cell subtype specific.…”

Section: Igg+ Plasma Cells Show Reduced Nfϰb Activationmentioning

confidence: 99%

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ReactomeGSA - Efficient Multi-Omics Comparative Pathway Analysis

Griss

Viteri

Sidiropoulos

et al. 2020

Preprint

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Pathway analyses are key methods to analyse ‘omics experiments. Nevertheless, integrating data from different ‘omics technologies and different species still requires considerable bioinformatics knowledge.Here we present the novel ReactomeGSA resource for comparative pathway analyses of multi-omics datasets. ReactomeGSA can be used through Reactome’s existing web interface and the novel ReactomeGSA R Bioconductor package with explicit support for scRNA-seq data. Data from different species is automatically mapped to a common pathway space. Public data from ExpressionAtlas and Single Cell ExpressionAtlas can be directly integrated in the analysis. ReactomeGSA thereby greatly reduces the technical barrier for multi-omics, cross-species, comparative pathway analyses.We used ReactomeGSA to characterise the role of B cells in anti-tumour immunity. We compared B cell rich and poor human cancer samples from five TCGA transcriptomics and two CPTAC proteomics studies. There, B cell-rich lung adenocarcinoma samples lack the otherwise present activation through NFkappaB. This may be linked to the presence of a specific subset of tumour associated IgG+ plasma cells that lack NFkappaB activation in scRNA-seq data from human melanoma. This showcases how ReactomeGSA can derive novel biomedical insights by integrating large multi-omics datasets.

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Section: Discussionsupporting

confidence: 77%

Section: Lung Adenocarcinomamentioning

confidence: 99%

Section: Lung Adenocarcinomamentioning

confidence: 99%

Section: Igg+ Plasma Cells Show Reduced Nfϰb Activationmentioning

confidence: 99%

See 2 more Smart Citations

ReactomeGSA - Efficient Multi-Omics Comparative Pathway Analysis

Griss

Viteri

Sidiropoulos

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

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“…Emerging evidence suggests that tumor-infiltrating B cells play an important role for the clinical outcome of anti-PD-1treated cancer patients. Thus, a higher frequency of melanomainfiltrating B cells with a plasmablast-like phenotype before therapy was associated with improved patient survival to anti-PD-1 treatment (64). More recently, Petitprez et al observed that the sarcoma immune class E, which is characterized by TLS containing T cells, follicular DCs, and a high density of B cells, is correlated with an improved response rate and survival to PD-1 blockade (65).…”

Section: Impact Of the Frequency Of Tumor-infiltrating B Cells And Tlmentioning

confidence: 99%

Characteristics of Tumor-Infiltrating Lymphocytes Prior to and During Immune Checkpoint Inhibitor Therapy

et al. 2020

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The tumor immune contexture plays a major role for the clinical outcome of patients. High densities of CD45RO + T helper 1 cells and CD8 + T cells are associated with improved survival of patients with various cancer entities. In contrast, a higher frequency of tumor-infiltrating M2 macrophages is correlated with poor prognosis. Recent studies provide evidence that the tumor immune architecture also essentially contributes to the clinical efficacy of immune checkpoint inhibitor (CPI) therapy in patients. Pretreatment melanoma samples from patients who experienced a clinical response to antiprogrammed cell death protein 1 (PD-1) treatment show higher densities of infiltrating CD8 + T cells compared to samples from patients that progressed during therapy. Anti-PD-1 therapy results in an increased density of tumor-infiltrating T lymphocytes in treatment responders. In addition, elevated frequencies of melanoma-infiltrating TCF7 + CD8 + T cells are correlated with beneficial clinical outcome of anti-PD-1-treated patients. In contrast, a high density of tumor-infiltrating, dysfunctional PD-1 + CD38 hi CD8 + cells in melanoma patients is associated with anti-PD-1 resistance. Such findings indicate that comprehensive tumor immune contexture profiling prior to and during CPI therapy may lead to the identification of underlying mechanisms for treatment response or resistance, and the design of improved immunotherapeutic strategies. Here, we focus on studies exploring the impact of intratumoral T and B cells at baseline on the clinical outcome of CPI-treated cancer patients. In addition, recent findings demonstrating the influence of CPIs on tumor-infiltrating lymphocytes are summarized.

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Therapeutic Cancer Vaccines for the Management of Recurrent and Metastatic Head and Neck Cancer

Ritter

Koirala

Wieland

et al. 2023

JAMA Otolaryngol Head Neck Surg

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ImportanceSquamous cell carcinoma of the head and neck (HNSCC) is prevalent globally and in the US. Management, particularly after disease recurrence, can be challenging, and exploring additional treatment modalities, such as therapeutic cancer vaccines, may offer an opportunity to improve outcomes in this setting.ObservationsThis review provides an overview of the clinical efficacy of different treatment modalities that are currently available for the treatment of recurrent and metastatic HNSCC, including checkpoint inhibitors and targeted therapies, with a detailed summary of the numerous T-cell vaccines that have been studied in the setting of HNSCC, as well as a detailed summary of B-cell therapeutic vaccines being investigated for various malignant tumors.Conclusions and RelevanceThe findings of this review suggest that several therapeutic T-cell and B-cell vaccines, which have been recently developed and evaluated in a clinical setting, offer a promising treatment modality with the potential to improve outcomes for patients with recurrent and metastatic HNSCC.

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B cells sustain inflammation and predict response to immune checkpoint blockade in human melanoma

Cited by 284 publications

References 93 publications

ReactomeGSA - Efficient Multi-Omics Comparative Pathway Analysis

ReactomeGSA - Efficient Multi-Omics Comparative Pathway Analysis

Characteristics of Tumor-Infiltrating Lymphocytes Prior to and During Immune Checkpoint Inhibitor Therapy

Therapeutic Cancer Vaccines for the Management of Recurrent and Metastatic Head and Neck Cancer

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