Complement Signals Determine Opposite Effects of B Cells in Chemotherapy-Induced Immunity

Lu, Yiwen; Zhao, Qiyi; Liao, Jian-You; Song, Erwei; Xia, Qi‐Dong; Pan, Jiayao; Li, Yihong; Li, Jiaqian; Zhou, Boxuan; Ye, Yingying; Di, Can; Yu, Shubin; Zeng, Yonghong; Su, Shicheng

doi:10.1016/j.cell.2020.02.015

Cited by 165 publications

(125 citation statements)

References 68 publications

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“…The interaction of C3 fragments with CR2 promotes the ICOS-L+ B cell generation. On the over hand, the over-expression of CD55 (a complement regulator) inhibits the complement activation and prevents the formation of ICOS-L+ B cell [51]. In this context, the activation of the classical pathway through the binding of the C1 complex and immunoglobulins produced by B cells, though, has not been investigated.…”

Section: Role Of Complement On Tumor Immunitymentioning

confidence: 99%

“…It allows complement activation but without the formation of the C5a anaphylatoxin and the membrane attack complex. On the other hand, it appeared that to have an effective response to treatment like chemotherapy and radiotherapy, a low level of complement activation is needed [49,51]. Another complement blocking agent is PMX53 that can block the C5aR1 and allow a reduction of the tumor size, in lung and melanoma mouse models.…”

Section: Complement Inhibitorsmentioning

confidence: 99%

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Complement System: Promoter or Suppressor of Cancer Progression?

et al. 2020

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Constituent of innate immunity, complement is present in the tumor microenvironment. The functions of complement include clearance of pathogens and maintenance of homeostasis, and as such could contribute to an anti-tumoral role in the context of certain cancers. However, multiple lines of evidence show that in many cancers, complement has pro-tumoral actions. The large number of complement molecules (over 30), the diversity of their functions (related or not to the complement cascade), and the variety of cancer types make the complement-cancer topic a very complex matter that has just started to be unraveled. With this review we highlight the context-dependent role of complement in cancer. Recent studies revealed that depending of the cancer type, complement can be pro or anti-tumoral and, even for the same type of cancer, different models presented opposite effects. We aim to clarify the current knowledge of the role of complement in human cancers and the insights from mouse models. Using our classification of human cancers based on the prognostic impact of the overexpression of complement genes, we emphasize the strong potential for therapeutic targeting the complement system in selected subgroups of cancer patients.

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Section: Role Of Complement On Tumor Immunitymentioning

confidence: 99%

Section: Complement Inhibitorsmentioning

confidence: 99%

Complement System: Promoter or Suppressor of Cancer Progression?

et al. 2020

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“…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%

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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“…74,78,79 Moreover, an ICOSL + B cell subset emerges in tumors after chemotherapy to elicit antitumor immunity. 77 However, an opposite effect of B cells in tumors is observed when tumor CD55 play predominant roles in the TME over the complement signals initiated by immunogenic cell death. 77 HOSSAIN ET AL.…”

Section: Immunosuppressive Cellsmentioning

confidence: 99%

Reinvigorating exhausted CD8⁺ cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy

Hossain

Liu

Dai

et al. 2020

Medicinal Research Reviews

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Immunotherapy has revolutionized the treatment of cancer in recent years and achieved overall success and long‐term clinical benefit in patients with a wide variety of cancer types. However, there is still a large proportion of patients exhibiting limited or no responses to immunotherapeutic strategy, some of which were even observed with hyperprogressive disease. One major obstacle restricting the efficacy is that tumor‐reactive CD8+ T cells, which are central for tumor control, undergo exhaustion, and lose their ability to eliminate cancer cells after infiltrating into the strongly immunosuppressive tumor microenvironment. Thus, as a potential therapeutic rationale in the development of cancer immunotherapy, targeting or reinvigorating exhausted CD8+ T cells has been attracting much interest. Hitherto, both intrinsic and extrinsic mechanisms that govern CD8+ T‐cell exhaustion have been explored. Specifically, the transcriptional and epigenetic landscapes have been depicted utilizing single‐cell RNA sequencing or mass cytometry (CyTOF). In addition, cellular metabolism dictating the tumor‐infiltrating CD8+ T‐cell fate is currently under investigation. A series of clinical trials are being carried out to further establish the current strategies targeting CD8+ T‐cell exhaustion. Taken together, despite the proven benefit of immunotherapy in cancer patients, additional efforts are still needed to fully circumvent limitations of exhausted T cells in the treatment. In this review, we will focus on the current cellular and molecular understanding of metabolic changes, epigenetic remodeling, and transcriptional regulation in CD8+ T‐cell exhaustion and describe hypothetical treatment approaches based on immunotherapy aiming at reinvigorating exhausted CD8+ T cells.

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Complement Signals Determine Opposite Effects of B Cells in Chemotherapy-Induced Immunity

Abstract: Highlights d A distinct B cell subset emerges in tumors after chemotherapy d B cells elicit anti-tumor T cell immunity by ICOSL d Complement signals initiated by immunogenic cell death shape B cell phenotypes d Tumor CD55 expression determines the opposite effects of B cells in tumors

Cited by 165 publications

References 68 publications

Complement System: Promoter or Suppressor of Cancer Progression?

Complement System: Promoter or Suppressor of Cancer Progression?

ReactomeGSA - Efficient Multi-Omics Comparative Pathway Analysis

Reinvigorating exhausted CD8⁺ cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy

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Complement Signals Determine Opposite Effects of B Cells in Chemotherapy-Induced Immunity

Abstract: Highlights d A distinct B cell subset emerges in tumors after chemotherapy d B cells elicit anti-tumor T cell immunity by ICOSL d Complement signals initiated by immunogenic cell death shape B cell phenotypes d Tumor CD55 expression determines the opposite effects of B cells in tumors

Cited by 165 publications

References 68 publications

Complement System: Promoter or Suppressor of Cancer Progression?

Complement System: Promoter or Suppressor of Cancer Progression?

ReactomeGSA - Efficient Multi-Omics Comparative Pathway Analysis

Reinvigorating exhausted CD8+ cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy

Contact Info

Product

Resources

About

Reinvigorating exhausted CD8⁺ cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy