Context-dependent roles of complement in cancer

Roumenina, Lubka T.; Daugan, Marie V.; Petitprez, Florent; Sautès-Fridman, Catheriné; Fridman, Wolf Herman

doi:10.1038/s41568-019-0210-0

Cited by 234 publications

(237 citation statements)

References 143 publications

(179 reference statements)

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“…Analysis of complement gene expression in thirty different cancers revealed consistent patterns of expression: a high expression of genes coding for classical and alternative pathway; high expression of regulators and a low expression of the lectin pathway and the terminal pathway genes [3]. These data suggest that the tumor could benefit from the early complement proteins but then sets up brakes to avoid any deleterious effector functions.…”

Section: Complement and Cancermentioning

confidence: 81%

“…The recruitment of immune cells inside the tumor is achieved thanks to the vascular network that also allows the recruitment of the components of the complement system. The complement system is often forgotten or underestimated, but it is a powerful inflammatory cascade and, as a part of innate immunity, it fully belongs to the TME [3]. The complement system is a set of more than thirty cell-bound or soluble proteins that can come inside the tumor via the circulation but also that can be produced by the tumor cells themselves and the infiltrated immune cells.…”

Section: Introductionmentioning

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: Complement and Cancermentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Complement System: Promoter or Suppressor of Cancer Progression?

et al. 2020

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“…The disease landscape emerging from these multi-factorial interactions is orchestrated by the three compartments, i.e., the cancer, the immune system, and the host. The outputs are numerous and include mainly: immunity that might control cancer and chronic inflammation that can be linked with tissue remodeling processes [40,41]. Inflammation is a hallmark of cancer and is mediated by immune cells attracted to or residing at sites of neoplastic transformation [42,43].…”

Section: Introductionmentioning

confidence: 99%

RKIP as an Inflammatory and Immune System Modulator: Implications in Cancer

et al. 2019

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Raf kinase inhibitor protein (RKIP), an important modulator of intracellular signalling pathways, is commonly downregulated in multiple cancers. This reduction, or loss of expression, is correlated not only with the presence of metastasis, contributing to RKIP’s classification as a metastasis suppressor, but also with tumour aggressiveness and poor prognosis. Recent findings suggest a strong involvement of RKIP in the modulation of tumour microenvironment components, particularly by controlling the infiltration of specific immune cells and secretion of pro-metastatic factors. Additionally, RKIP interaction with multiple signalling molecules seems to potentiate its function as a regulator of inflammatory processes, mainly through stimulation of anti- or pro-inflammatory cytokines. Furthermore, RKIP is involved in the modulation of immunotherapeutic drugs response, through diverse mechanisms that sensitize cells to apoptosis. In the present review, we will provide updated information about the role of RKIP as an inflammatory and immune modulator and its potential implications in cancer will be addressed.

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“…The complement system plays also a pivotal role in promoting the metastatic spread by regulating the recruitment of myeloid cells and MDSCs in lung and regulating the release of IL10 and TGF-β with subsequent suppression of effector CD8 and CD4 T lymphocytes and induction of Treg generation (122) in a breast cancer preclinical model. Moreover, in absence of tumor specific T cells, the anaphylatoxin C5a promotes tumor growth by recruiting and activating myeloid-derived suppressor cells to release NO and ROS (123,124). However, it was recently demonstrated that C3a and C5a have a pleiotropic and context specific role in tumor progression.…”

Section: Mdscs Promote Primary Tumor Growth and Local Invasionmentioning

confidence: 99%

The Engagement Between MDSCs and Metastases: Partners in Crime

et al. 2020

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Tumor metastases represent the major cause of cancer-related mortality, confirming the urgent need to identify key molecular pathways and cell-associated networks during the early phases of the metastatic process to develop new strategies to either prevent or control distal cancer spread. Several data revealed the ability of cancer cells to establish a favorable microenvironment, before their arrival in distant organs, by manipulating the cell composition and function of the new host tissue where cancer cells can survive and outgrow. This predetermined environment is termed "pre-metastatic niche" (pMN). pMN development requires that tumor-derived soluble factors, like cytokines, growth-factors and extracellular vesicles, genetically and epigenetically reprogram not only resident cells (i.e., fibroblasts) but also non-resident cells such as bone marrow-derived cells. Indeed, by promoting an "emergency" myelopoiesis, cancer cells switch the steady state production of blood cells toward the generation of pro-tumor circulating myeloid cells defined as myeloid-derived suppressor cells (MDSCs) able to sustain tumor growth and dissemination. MDSCs are a heterogeneous subset of myeloid cells with immunosuppressive properties that sustain metastatic process. In this review, we discuss current understandings of how MDSCs shape and promote metastatic dissemination acting in each fundamental steps of cancer progression from primary tumor to metastatic disease.

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Context-dependent roles of complement in cancer

Cited by 234 publications

References 143 publications

Complement System: Promoter or Suppressor of Cancer Progression?

Complement System: Promoter or Suppressor of Cancer Progression?

RKIP as an Inflammatory and Immune System Modulator: Implications in Cancer

The Engagement Between MDSCs and Metastases: Partners in Crime

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