Never Travel Alone: The Crosstalk of Circulating Tumor Cells and the Blood Microenvironment

Heeke, Simon; Mograbi, Baharia; Alix‐Panabières, Catherine; Hofman, Paul

doi:10.3390/cells8070714

Cited by 105 publications

(114 citation statements)

References 85 publications

(122 reference statements)

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“…The identification of heterotypic CTC clusters supports this possibility. Interaction between tumor detached cells and macrophages can induce local inflammation that favors local extracellular matrix remodeling and CTC cluster migration ( [17] for review). This tight crosstalk between macrophages and CTCs can even result into cell fusion (hybrid CTCs) that enhances invasiveness in glioblastoma [18].…”

Section: Origin and Dissemination Of Ctc Clustermentioning

confidence: 99%

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Circulating Tumor Cell Clusters: United We Stand Divided We Fall

Amintas

Bedel

Moreau‐Gaudry

et al. 2020

IJMS

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The presence of circulating tumor cells (CTCs) and CTC clusters, also known as tumor microemboli, in biological fluids has long been described. Intensive research on single CTCs has made a significant contribution in understanding tumor invasion, metastasis tropism, and intra-tumor heterogeneity. Moreover, their being minimally invasive biomarkers has positioned them for diagnosis, prognosis, and recurrence monitoring tools. Initially, CTC clusters were out of focus, but major recent advances in the knowledge of their biogenesis and dissemination reposition them as critical actors in the pathophysiology of cancer, especially metastasis. Increasing evidence suggests that “united” CTCs, organized in clusters, resist better and carry stronger metastatic capacities than “divided” single CTCs. This review gathers recent insight on CTC cluster origin and dissemination. We will focus on their distinct molecular package necessary to resist multiple cell deaths that all circulating cells normally face. We will describe the molecular basis of their increased metastatic potential as compared to single CTCs. We will consider their clinical relevance as prognostic biomarkers. Finally, we will propose future directions for research and clinical applications in this promising topic in cancer.

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Section: Origin and Dissemination Of Ctc Clustermentioning

confidence: 99%

“…Once in the circulation, single CTCs have been extensively described to setup interaction with platelets [17]. Association of CTCs in clusters appears to confer CTCs many advantages ( Figure 1).…”

Section: Origin and Dissemination Of Ctc Clustermentioning

confidence: 99%

Circulating Tumor Cell Clusters: United We Stand Divided We Fall

Amintas

Bedel

Moreau‐Gaudry

et al. 2020

IJMS

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“…One option to avoid the fatal encounter is to generate clusters. CTC clusters have been detected both in tumor-bearing mice and in cancer patients, and even though they represent a minority (2-4%) of the entire CTC population, they have higher probability to generate metastases than "lonely" CTCs (136). The CTC clusters escape the immune surveillance by physically interacting between themselves (homotypic interaction) or with leukocytes (heterotopic interaction).…”

Section: Mdscs Protect Ctcs In Circulation and Promote Their Extravasmentioning

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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“…CTCs closely interact with circulating immune cells, such as neutrophils and macrophages, to survive in the blood stream [100], and extravasion of tumor cells into the circulation is supported by immune cells. BC patients who harbored CTCs exhibited more intra-tumoral and peri-tumoral regulatory T cells than BC patients with no CTCs [101].…”

Section: Circulating Tumor Cellsmentioning

confidence: 99%

Liquid Biopsies to Evaluate Immunogenicity of Gynecological/Breast Tumors: On the Way to Blood-Based Biomarkers for Immunotherapies

Keup

Kasimir‐Bauer

2020

Breast Care

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Background: Despite the assumption of breast cancer (BC) as a cold, non-immunogenic tumor, immune checkpoint inhibitor (ICI) therapy is favorable for a subgroup of patients. Immunohistochemical assessment of the programmed cell death ligand 1 (PD-L1) is the only approved companion diagnostic for anti-PD-L1 therapy in metastatic triple-negative BC; however, challenges regarding the standardization of PD-L1 scoring in tumor tissue still remain. Consequently, to select patients most likely to respond to ICI, blood-based biomarkers are urgently needed. Summary and Key Messages: Liquid biopsy, comprising circulating immune cells, circulating tumor cells and extracellular vesicles, as well as their surface proteins, is of high potential, and these analytes were already shown to be molecular correlates or regulators of the evasion from antitumoral immune reaction. Liquid biopsy, also enabling the evaluation of tumor mutational burden (TMB), microsatellite instability, and the T-cell receptor repertoire, allows serial sampling for monitoring purposes and reflects intra-tumoral heterogeneity which qualifies as marker for immunogenicity. Only a very few studies have already elucidated the potential of these analytes as biomarkers under ICI therapy. Nonetheless, the topic is of growing interest and has high relevance for the future. However, for clinical implementation, these multifarious analytes first need to pass robust standardization and validation procedures.

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Never Travel Alone: The Crosstalk of Circulating Tumor Cells and the Blood Microenvironment

Cited by 105 publications

References 85 publications

Circulating Tumor Cell Clusters: United We Stand Divided We Fall

Circulating Tumor Cell Clusters: United We Stand Divided We Fall

The Engagement Between MDSCs and Metastases: Partners in Crime

Liquid Biopsies to Evaluate Immunogenicity of Gynecological/Breast Tumors: On the Way to Blood-Based Biomarkers for Immunotherapies

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