Beyond the tumour microenvironment

Laplane, Lucie; Duluc, Dorothée; Bikfalvi, Andréas; Larmonier, Nicolas; Pradeu, Thomas

doi:10.1002/ijc.32343

Cited by 78 publications

(57 citation statements)

References 88 publications

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“…Thus, a concern exists on whether TME is sufficiently comprehensive to reflect true situations and serve as an effective target for cancer treatment. 5 Laplane et al 5 , 6 introduced a term called tumor organismal environment (TOE), representing microenvironments that are distant from the lesions of cancer but can affect its development. Considering the lack of consensus in defining TME combined with the fact that the tumor environment (TE) of different locations may differ greatly, they also divided TE into six layers, including tumor cell to tumor-cell environment (TCTCE), niche, confined TE, proximal TE, peripheral TE, and TOE.…”

Section: Persistent Updating Concept Of Tmementioning

confidence: 99%

The updated landscape of tumor microenvironment and drug repurposing

Jin

2020

Sig Transduct Target Ther

634

483

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Accumulating evidence shows that cellular and acellular components in tumor microenvironment (TME) can reprogram tumor initiation, growth, invasion, metastasis, and response to therapies. Cancer research and treatment have switched from a cancer-centric model to a TME-centric one, considering the increasing significance of TME in cancer biology. Nonetheless, the clinical efficacy of therapeutic strategies targeting TME, especially the specific cells or pathways of TME, remains unsatisfactory. Classifying the chemopathological characteristics of TME and crosstalk among one another can greatly benefit further studies exploring effective treating methods. Herein, we present an updated image of TME with emphasis on hypoxic niche, immune microenvironment, metabolism microenvironment, acidic niche, innervated niche, and mechanical microenvironment. We then summarize conventional drugs including aspirin, celecoxib, β-adrenergic antagonist, metformin, and statin in new antitumor application. These drugs are considered as viable candidates for combination therapy due to their antitumor activity and extensive use in clinical practice. We also provide our outlook on directions and potential applications of TME theory. This review depicts a comprehensive and vivid landscape of TME from biology to treatment.

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Section: Persistent Updating Concept Of Tmementioning

confidence: 99%

The updated landscape of tumor microenvironment and drug repurposing

Jin

2020

Sig Transduct Target Ther

634

483

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“…In addition, the SNS innervation of bone marrow (BM) seems to play a regulatory role in hematopoiesis and immunological function. Sympathetic neurotransmitters act on ARs expressed on BM niche cells controlling the maintenance of healthy hematopoietic stem cells (HSCs) and their mobilization into peripheral blood [52,53]. BM is commonly affected by metastasis and its dense sympathetic innervation seems to be related to this observation.…”

Section: Discussionmentioning

confidence: 99%

“…Increased sympathetic activity facilitated the colonization of circulating tumor cells through an increase in blood vessel density [ 54 ]. Nonetheless, the action of SNS on bone marrow is complex and myeloproliferative neoplasms and acute myelogenous leukemia have been related to a degradation of the bone marrow SNS innervation which favors the proliferation of the mutated cells over the HSCs [ 53 , 55 ]. The bulk of evidence demonstrating the effect of SNS and HPA axis activation on immune responses and immune cells is nicely summarized in the recent review of Colon-Echevarria et al.…”

Section: Discussionmentioning

confidence: 99%

Does sympathetic nervous system modulate tumor progression? A narrative review of the literature

Stavropoulos

Sarantopoulos

Liverezas

2020

Journal of Drug Assessment

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Objective: The role of the sympathetic nervous system (SNS) in tumor development, progression and metastasis is studied for more than half a century and is attracting more attention during the last years. In this narrative review, we aim to a chronological and methodological presentation of the most interesting and pioneering studies on the subject. Methods: The complexity of the autonomic nervous system's interaction with the immune system, its direct and indirect effects on tumors and their surrounding tissues, plus the diversity and heterogeneity in the design and methodology of the studies, provide hard-to-interpret data and, at times, controversial findings. Studies are categorized into four main groups regarding the distribution of sympathetic nerve fibers inside the tumor, the effect of sympathectomy on cancer progression, the role of neurotransmitters on tumor growth and the impact of sympathetic adrenergic signaling on the anti-tumor immune response. Results: Studies from all four categories converge to a common point. There is strong evidence that SNS function plays a role in the development and progression of tumors and subsequently the modification of SNS function, locally or diffusely, can affect the course of tumor growth. Conclusion: The impact of SNS function on cancer behavior may be exerted in two ways, directly via the sympathetic nerve fibers or through widely distributed neurotransmitters. Modification of them, combined or not with treatments altering the immune function, could be the target for future therapeutic implications.

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“…Thus, cancer is also a systemic disease [ 23 ], and even tumor-targeted immunotherapies require systemic immune responses to be effective [ 24 ]. Therefore, the comprehensive view of the immune system in the context of the whole organism (the so-called “tumor organismal environment” [ 25 ]) should be considered. We will review hereafter the contribution of systemic elements not located in the TME but which can substantially affect tumor development and immunotherapy success, including soluble factors and circulating cell populations with a special focus on the role of PD-L1 as a major immune regulator ( Table 1 ).…”

Section: Systemic Biomarkers and Pd-l1/pd-1 As Potential Systemic mentioning

confidence: 99%

PD-L1 in Systemic Immunity: Unraveling Its Contribution to PD-1/PD-L1 Blockade Immunotherapy

Bocanegra

Blanco

Fernández-Hinojal

et al. 2020

IJMS

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The use of monoclonal antibodies targeting PD-1/PD-L1 axis completely changed anticancer treatment strategies. However, despite the significant improvement in overall survival and progression-free survival of patients undergoing these immunotherapy treatments, the only clinically accepted biomarker with some prediction capabilities for the outcome of the treatment is PD-L1 expression in tumor biopsies. Nevertheless, even when having PD-L1-positive tumors, numerous patients do not respond to these treatments. Considering the high cost of these therapies and the risk of immune-related adverse events during therapy, it is necessary to identify additional biomarkers that would facilitate stratifying patients in potential responders and non-responders before the start of immunotherapies. Here, we review the utility of PD-L1 expression not only in tumor cells but in immune system cells and their influence on the antitumor activity of immune cell subsets.

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Beyond the tumour microenvironment

Cited by 78 publications

References 88 publications

The updated landscape of tumor microenvironment and drug repurposing

The updated landscape of tumor microenvironment and drug repurposing

Does sympathetic nervous system modulate tumor progression? A narrative review of the literature

PD-L1 in Systemic Immunity: Unraveling Its Contribution to PD-1/PD-L1 Blockade Immunotherapy

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