Pleomorphic Sarcomas

Carvalho, Sofia Daniela; Pissaloux, Daniel; Crombé, Amandine; Coindre, Jean‐Michel; Loarer, François Le

doi:10.1016/j.path.2018.10.004

Cited by 29 publications

(7 citation statements)

References 100 publications

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“…In order to identify how tumor size and depth influences tumor immune cell infiltration, we developed a systematic platform to prospectively characterize the tumor-immune microenvironment of a single STS subtype, undifferentiated pleomorphic sarcoma (UPS). UPS is one the most common adult STS subtypes and is associated with responses to immune checkpoint inhibitors [10][11][12][13]. Furthermore, focused analysis on UPS tumors limits inter-tumoral heterogeneity and enables direct histological and clinical comparisons.…”

Section: Introductionmentioning

confidence: 99%

Tumor morphology and location associate with immune cell composition in pleomorphic sarcoma

Wustrack

Shao

Sheridan

et al. 2021

Cancer Immunol Immunother

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Background Soft-tissue sarcomas (STS) are a rare group of mesenchymal malignancies that account for approximately 1% of adult human cancer. Undifferentiated pleomorphic sarcoma (UPS) is one of the most common subtypes of adult STS. Clinical stratification of UPS patients has not evolved for decades and continues to rely on tumor-centric metrics including tumor size and depth. Our understanding of how the tumor microenvironment correlates to these clinicopathologic parameters remains limited. Methods Here, we performed single-cell flow cytometric immune-based profiling of 15 freshly resected UPS tumors and integrated this analysis with clinical, histopathologic, and outcomes data using both a prospective and retrospective cohort of UPS patients. Results We uncovered a correlation between physiologic and anatomic properties of UPS tumors and the composition of immune cells in the tumor microenvironment. Specifically, we identified an inverse correlation between tumor-infiltrating CD8 + T cells and UPS tumor size; and a positive correlation between tumor-infiltrating CD8 + T cells and overall survival. Moreover, we demonstrate an association between anatomical location (deep or superficial) and frequency of CD4 + PD1hi infiltrating T cells in UPS tumors. Conclusions Our study provides an immune-based analysis of the tumor microenvironment in UPS patients and describes the different composition of tumor infiltrating lymphocytes based on size and tumor depth.

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Section: Introductionmentioning

confidence: 99%

Tumor morphology and location associate with immune cell composition in pleomorphic sarcoma

Wustrack

Shao

Sheridan

et al. 2021

Cancer Immunol Immunother

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“…PLPS are similar to UPS at the genomic level, where multiple alterations occur and RB1 is frequently lost. However, unlike UPS, these tumors are not known to have amplification in MDM2 [37,71].…”

Section: Liposarcoma (Lps)mentioning

confidence: 99%

“…UPS (formerly called malignant fibrous histiocytoma) accounts for 15-20% of all soft tissue sarcomas (STS) and normally occurs in the limbs and trunk of adults >40 years of age [37]. UPS falls into the category of "a complex karyotype sarcoma" and is characterized by a lack of a line of differentiation.…”

Section: Undifferentiated Pleomorphic Sarcoma (Ups)mentioning

confidence: 99%

“…Trp53 deletion results in poorly differentiated soft tissue sarcomas [132]; however, a true EwS mouse model is yet to be developed [49]. [36,38,39], MFS [36,59], PLPS [37,66], LMS [36,37,74], CS [101], OS [116,118], EwS [130], MPNST [82] CDKN2A p16 INK4a and ARF Deletion, Mutation UPS [36,40], MFS [36,59], LMS [75], MPNST [36,[77][78][79][80]82,[133][134][135][136][137][138], CS [101], ARMS [139], OS [116,118], EwS [130] CDKN2B p15 INK4b Deletion MFS [36,59], MPNST [36,134,136] CCND1-3 Cyclin D1-3 Amplification MFS [59], LMS [75], CS [101], OS …”

Section: Ewing Sarcoma (Ews)mentioning

confidence: 99%

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CDKs in Sarcoma: Mediators of Disease and Emerging Therapeutic Targets

Kohlmeyer

Gordon

Tanas

et al. 2020

IJMS

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Sarcomas represent one of the most challenging tumor types to treat due to their diverse nature and our incomplete understanding of their underlying biology. Recent work suggests cyclin-dependent kinase (CDK) pathway activation is a powerful driver of sarcomagenesis. CDK proteins participate in numerous cellular processes required for normal cell function, but their dysregulation is a hallmark of many pathologies including cancer. The contributions and significance of aberrant CDK activity to sarcoma development, however, is only partly understood. Here, we describe what is known about CDK-related alterations in the most common subtypes of sarcoma and highlight areas that warrant further investigation. As disruptions in CDK pathways appear in most, if not all, subtypes of sarcoma, we discuss the history and value of pharmacologically targeting CDKs to combat these tumors. The goals of this review are to (1) assess the prevalence and importance of CDK pathway alterations in sarcomas, (2) highlight the gap in knowledge for certain CDKs in these tumors, and (3) provide insight into studies focused on CDK inhibition for sarcoma treatment. Overall, growing evidence demonstrates a crucial role for activated CDKs in sarcoma development and as important targets for sarcoma therapy.

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“…They account for 14% of all adult STSs, and about 60% occur in the extremities. Nevertheless, they can grow anywhere in the human body [ 105 , 106 ]. Up to 78% of UPS tumors have a deletion of the Rb1 gene due to a loss of regions within chr13q [ 107 , 108 ].…”

Section: Cdk Pathway Dysregulation In Prevalent Stssmentioning

confidence: 99%

The Role of CDK Pathway Dysregulation and Its Therapeutic Potential in Soft Tissue Sarcoma

Thiel

Daigeler

Kolbenschlag

et al. 2022

Cancers

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Soft tissue sarcomas (STSs) are tumors that are challenging to treat due to their pathologic and molecular heterogeneity and their tumor biology that is not yet fully understood. Recent research indicates that dysregulation of cyclin-dependent kinase (CDK) signaling pathways can be a strong driver of sarcogenesis. CDKs are enzyme forms that play a crucial role in cell-cycle control and transcription. They belong to the protein kinases group and to the serine/threonine kinases subgroup. Recently identified CDK/cyclin complexes and established CDK/cyclin complexes that regulate the cell cycle are involved in the regulation of gene expression through phosphorylation of critical components of transcription and pre-mRNA processing mechanisms. The current and continually growing body of data shows that CDKs play a decisive role in tumor development and are involved in the proliferation and growth of sarcoma cells. Since the abnormal expression or activation of large numbers of CDKs is considered to be characteristic of cancer development and progression, dysregulation of the CDK signaling pathways occurs in many subtypes of STSs. This review discusses how reversal and regulation can be achieved with new therapeutics and summarizes the current evidence from studies regarding CDK modulation for STS treatment.

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Pleomorphic Sarcomas

Cited by 29 publications

References 100 publications

Tumor morphology and location associate with immune cell composition in pleomorphic sarcoma

Tumor morphology and location associate with immune cell composition in pleomorphic sarcoma

CDKs in Sarcoma: Mediators of Disease and Emerging Therapeutic Targets

The Role of CDK Pathway Dysregulation and Its Therapeutic Potential in Soft Tissue Sarcoma

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