Role of extracellular matrix architecture and signaling in melanoma therapeutic resistance

Popović, Aleksandra; Tartare‐Deckert, Sophie

doi:10.3389/fonc.2022.924553

Cited by 10 publications

(4 citation statements)

References 146 publications

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“…19 20 The composition and architecture of fibrotic stroma may be of greater importance than the quantity present. 21 Along these lines, our RC identified six key mechanisms of interest potentially associated with immune exclusion irrespective of cancer and tumor type. These included: (1) lack of chemotactic factors, (2) a mechanical barrier, (3) immunosuppressive cytokines, (4) cancer-associated fibroblast subtypes, (5) disordered vasculature and ( 6) apoptosis of T cells.…”

Section: Discussionmentioning

confidence: 88%

Developing a definition of immune exclusion in cancer: results of a modified Delphi workshop

Clifton

Rothenberg

Ascierto

et al. 2023

J Immunother Cancer

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Checkpoint inhibitors represent an effective treatment approach for a variety of cancers through their inhibition of immune regulatory pathways within the tumor microenvironment (TME). Unfortunately only a minority of patients with cancer achieve clinical benefit from immunotherapy, with the TME emerging as an important predictor of outcomes and sensitivity to therapy. The extent and pattern of T-cell infiltration can vary prominently within/across tumors and represents a biological continuum. Three immune profiles have been identified along this continuum: ‘immune-desert’ or ‘T-cell cold’ phenotype, ‘immune-active’, ‘inflamed’, or ‘T-cell hot’ phenotype, and ‘immune excluded’ phenotype. Of the three profiles, immune excluded remains the most ill-defined with no clear, universally accepted definition even though it is commonly associated with lack of response to immune checkpoint inhibitors and poor clinical outcomes. To address this, 16 multidisciplinary cancer experts from around the world were invited to participate in a symposium using a three-round modified Delphi approach. The first round was an open-ended questionnaire distributed via email and the second was an in-person discussion of the first round results that allowed for statements to be revised as necessary to achieve a maximum consensus (75% agreement) among the rating committee (RC). The final round questionnaire was distributed to the RC via email and had a 100% completion rate. The Delphi process resulted in moving us closer to a consensus definition for immune exclusion that is practical, clinically pertinent, and applicable across a wide range of cancer histologies. A general consensus of the role of immune exclusion in resistance to checkpoint therapy and five research priorities emerged from this process. Together, these tools could help efforts designed to address the underlying mechanisms of immune exclusion that span cancer types and, ultimately, aid in the development of treatments to target these mechanisms to improve patient outcomes.

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Section: Discussionmentioning

confidence: 88%

Developing a definition of immune exclusion in cancer: results of a modified Delphi workshop

Clifton

Rothenberg

Ascierto

et al. 2023

J Immunother Cancer

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“…Over the past decade, the ECM in the tumor microenvironment has been shown to play a key role in the progression and acquisition of therapeutic resistance in melanoma [ 51 , 52 ]. Although TT and ICB have improved overall survival in patients with metastatic cutaneous melanoma [ 27 ], therapeutic resistance, which involves both tumor cell intrinsic mechanisms and extrinsic cues from the tumor microenvironment, constitutes a major hurdle in the successful treatment of melanoma.…”

Section: The Matrix Revolution: Tumor Microenvironment Remodeling In ...mentioning

confidence: 99%

The mechanical phenotypic plasticity of melanoma cell: an emerging driver of therapy cross-resistance

2023

Self Cite

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Advanced cutaneous melanoma is the deadliest form of skin cancer and one of the most aggressive human cancers. Targeted therapies (TT) against BRAF mutated melanoma and immune checkpoints blockade therapies (ICB) have been a breakthrough in the treatment of metastatic melanoma. However, therapy-driven resistance remains a major hurdle in the clinical management of the metastatic disease. Besides shaping the tumor microenvironment, current treatments impact transition states to promote melanoma cell phenotypic plasticity and intratumor heterogeneity, which compromise treatment efficacy and clinical outcomes. In this context, mesenchymal-like dedifferentiated melanoma cells exhibit a remarkable ability to autonomously assemble their own extracellular matrix (ECM) and to biomechanically adapt in response to therapeutic insults, thereby fueling tumor relapse. Here, we review recent studies that highlight mechanical phenotypic plasticity of melanoma cells as a hallmark of adaptive and non-genetic resistance to treatment and emerging driver in cross-resistance to TT and ICB. We also discuss how targeting BRAF-mutant dedifferentiated cells and ECM-based mechanotransduction pathways may overcome melanoma cross-resistance.

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“…Melanoma is the most severe type of skin cancer with a poor prognosis and high mortality rate. Current therapeutic approaches are unable to target tumor cells due to increased stiffness resulting from abnormal extracellular matrix structural changes and a hypoxic tumor environment [ 200 ]. In this regard, the ability of L. lactis to detect melanoma using Multispectral Optoacoustic Tomography (MSOT) was investigated [ 156 ].…”

Section: Engineered Bacteria As Imaging Vectorsmentioning

confidence: 99%

Engineered live bacteria as disease detection and diagnosis tools

Tanniche,

Behkam

2023

J Biol Eng

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Sensitive and minimally invasive medical diagnostics are essential to the early detection of diseases, monitoring their progression and response to treatment. Engineered bacteria as live sensors are being developed as a new class of biosensors for sensitive, robust, noninvasive, and in situ detection of disease onset at low cost. Akin to microrobotic systems, a combination of simple genetic rules, basic logic gates, and complex synthetic bioengineering principles are used to program bacterial vectors as living machines for detecting biomarkers of diseases, some of which cannot be detected with other sensing technologies. Bacterial whole-cell biosensors (BWCBs) can have wide-ranging functions from detection only, to detection and recording, to closed-loop detection-regulated treatment. In this review article, we first summarize the unique benefits of bacteria as living sensors. We then describe the different bacteria-based diagnosis approaches and provide examples of diagnosing various diseases and disorders. We also discuss the use of bacteria as imaging vectors for disease detection and image-guided surgery. We conclude by highlighting current challenges and opportunities for further exploration toward clinical translation of these bacteria-based systems.

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Role of extracellular matrix architecture and signaling in melanoma therapeutic resistance

Cited by 10 publications

References 146 publications

Developing a definition of immune exclusion in cancer: results of a modified Delphi workshop

Developing a definition of immune exclusion in cancer: results of a modified Delphi workshop

The mechanical phenotypic plasticity of melanoma cell: an emerging driver of therapy cross-resistance

Engineered live bacteria as disease detection and diagnosis tools

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