PLCG2 as a potential indicator of tumor microenvironment remodeling in soft tissue sarcoma

Abstract Background: Soft tissue sarcoma is a malignant tumor with high degree of malignancy and poor prognosis, originating from mesenchymal tissue. Long non-coding RNAs (lncRNAs) are involved in various biological and pathological processes in the body. They target mRNA through transcription or post-transcription, resulting in the occurrence, invasion, and metastasis of tumors. Therefore, they are highly relevant with regard to early diagnoses and as prognostic indicators.Objective: The objective of the present study was to identify immune-related lncRNAs associated with the tumor microenvironment that can be used to predict soft tissue sarcomas.Methods: Clinical data and follow-up data were obtained from the cBioPortal database, and RNA sequencing data used for the model structure can be accessed from. The Cancer Genome Atlas (TCGA) database. LncRNAs were screened by differential expression analysis and co-expression analysis. The Cox regression model and Kaplan–Meier analysis were used to study the association between lncRNAs and soft tissue sarcoma prognosis in the immune microenvironment. Unsupervised cluster analysis was then completed to discover the impact of screening lncRNAs on disease. Lastly, we constructed an mRNA-lncRNA network by Cytoscape software.Results: Unsupervised cluster analysis revealed that the 210 lncRNAs screened showed strong correlation with the tumor immune microenvironment. Two signatures containing seven and five lncRNAs related to the tumor microenvironment were constructed and used to predict overall survival (OS) and disease-free survival (DFS). The Kaplan–Meier（K-M） survival curve showed that the prognoses of patients in the high-risk and low-risk groups differed significantly, and the prognosis associated with the low-risk group was better than that associated with the high-risk group. Two nomograms with predictive capabilities were established.Conclusion: The results indicate that seven OS- and five DFS-related lncRNAs are correlated with the prognosis of soft tissue sarcoma.

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Addressing the Adult Soft Tissue Sarcoma Microenvironment with Intratumoral Immunotherapy

Sarcoma ◽

10.1155/2018/9305294 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Shailaja Raj ◽

Lance D. Miller ◽

Pierre L. Triozzi

Keyword(s):

Soft Tissue ◽

Tumor Microenvironment ◽

Soft Tissue Sarcoma ◽

Immune Cells ◽

Crucial Role ◽

Dynamic Equilibrium ◽

Heterogeneous Group ◽

Complex Interactions

Sarcoma is comprised of a heterogeneous group of tumors originating from the mesenchyme. Sarcoma is also the first tumor that responded to immunotherapeutic agents often termed as “Coley’s toxins.” However, immunotherapy is yet to establish its presence in sarcomas. Complex interactions between tumor and immune cells in the tumor microenvironment play a crucial role in response to immunotherapy. There is a dynamic equilibrium created by the immune cells infiltrating the tumor, and this forms the basis of tumor evasion. Manipulating the intratumoral microenvironment will help overcome tumor evasion.

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CD11c-CD8 Spatial Cross Presentation: A Novel Approach to Link Immune Surveillance and Patient Survival in Soft Tissue Sarcoma

Cancers ◽

10.3390/cancers13051175 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1175

Author(s):

Yanhong Su ◽

Panagiotis Tsagkozis ◽

Andri Papakonstantinou ◽

Nicholas P. Tobin ◽

Okan Gultekin ◽

...

Keyword(s):

Soft Tissue ◽

Tumor Microenvironment ◽

Soft Tissue Sarcoma ◽

Patient Survival ◽

Immune Surveillance ◽

Multivariable Analysis ◽

Predictive Biomarkers ◽

University Hospital ◽

Immune Reactivity ◽

Cross Presentation

Checkpoint inhibitors are slowly being introduced in the care of specific sarcoma subtypes such as undifferentiated pleomorphic sarcoma, alveolar soft part sarcoma, and angiosarcoma even though formal indication is lacking. Proper biomarkers to unravel potential immune reactivity in the tumor microenvironment are therefore expected to be highly warranted. In this study, intratumoral spatial cross presentation was investigated as a novel concept where immune cell composition in the tumor microenvironment was suggested to act as a proxy for immune surveillance. Double immunohistochemistry revealed a prognostic role of direct spatial interactions between CD11c+ antigen-presenting cells (APCs) and CD8+ cells in contrast to each marker alone in a soft tissue sarcoma (STS) cohort of 177 patients from the Karolinska University Hospital (MFS p = 0.048, OS p = 0.025). The survival benefit was verified in multivariable analysis (MFS p = 0.012, OS p = 0.004). Transcriptomics performed in the TCGA sarcoma cohort confirmed the prognostic value of combining CD11c with CD8 (259 patients, p = 0.005), irrespective of FOXP3 levels and in a CD274 (PD-LI)-rich tumor microenvironment. Altogether, this study presents a histopathological approach to link immune surveillance and patient survival in STS. Notably, spatial cross presentation as a prognostic marker is distinct from therapy response-predictive biomarkers such as immune checkpoint molecules of the PD-L1/PD1 pathway.

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Multiplexed Evaluation of Microdosed Antineoplastic Agents In Situ in the Tumor Microenvironment of Patients with Soft Tissue Sarcoma

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-20-0614 ◽

2020 ◽

Vol 26 (15) ◽

pp. 3958-3968 ◽

Cited By ~ 2

Author(s):

Kenneth R. Gundle ◽

Gary B. Deutsch ◽

Howard J. Goodman ◽

Seth M. Pollack ◽

Matthew J. Thompson ◽

...

Keyword(s):

Soft Tissue ◽

Tumor Microenvironment ◽

Soft Tissue Sarcoma ◽

Antineoplastic Agents

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Morphological Examination of a Herpes-type Virus Indigenous for Tree Shrews

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100067790 ◽

1970 ◽

Vol 28 ◽

pp. 160-161

Author(s):

J. P. Brunschwig ◽

R. M. McCombs ◽

R. Mirkovic ◽

M. Benyesh-Melnick

Keyword(s):

Electron Microscopy ◽

Soft Tissue ◽

Chick Embryo ◽

Soft Tissue Sarcoma ◽

Cell Cultures ◽

Tree Shrew ◽

Type Virus ◽

Morphological Examination ◽

Tree Shrews ◽

Embryo Cells

A new virus, established as a member of the herpesvirus group by electron microscopy, was isolated from spontaneously degenerating cell cultures derived from the kidneys and lungs of two normal tree shrews. The virus was found to replicate best in cells derived from the homologous species. The cells used were a tree shrew cell line, T-23, which was derived from a spontaneous soft tissue sarcoma. The virus did not multiply or did so poorly for a limited number of passages in human, monkey, rodent, rabbit or chick embryo cells. In the T-23 cells, the virus behaved as members of the subgroup B of herpesvirus, in that the virus remained primarily cell associated.

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