دورية أكاديمية
أعرض في EDS

The immune landscape of undifferentiated pleomorphic sarcoma.

التفاصيل البيبلوغرافية
العنوان: The immune landscape of undifferentiated pleomorphic sarcoma.
المؤلفون: Lazcano R; Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Barreto CM; Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Salazar R; Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Carapeto F; Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Traweek RS; Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Leung CH; Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Gite S; Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Mehta J; Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Ingram DR; Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Wani KM; Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Vu KT; Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Parra ER; Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Lu W; Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Zhou J; Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Witt RG; Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Cope B; Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Thirasastr P; Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Lin HY; Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Scally CP; Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Conley AP; Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Ratan R; Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Livingston JA; Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Zarzour AM; Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Ludwig J; Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Araujo D; Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Ravi V; Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Patel S; Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Benjamin R; Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Wargo J; Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Wistuba II; Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.; Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.; Division of Pathology and Laboratory Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX, United States., Somaiah N; Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Roland CL; Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Keung EZ; Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Solis L; Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Wang WL; Division of Pathology and Laboratory Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX, United States., Lazar AJ; Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.; Division of Pathology and Laboratory Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX, United States.; Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Nassif EF; Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
المصدر: Frontiers in oncology [Front Oncol] 2022 Oct 12; Vol. 12, pp. 1008484. Date of Electronic Publication: 2022 Oct 12 (Print Publication: 2022).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101568867 Publication Model: eCollection Cited Medium: Print ISSN: 2234-943X (Print) Linking ISSN: 2234943X NLM ISO Abbreviation: Front Oncol Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Lausanne : Frontiers Research Foundation]
مستخلص: Introduction: Undifferentiated pleomorphic sarcoma (UPS) can be associated with a relatively dense immune infiltration. Immune checkpoint inhibitors (anti-PD1, anti-PDL1, and anti-CTLA4) are effective in 20% of UPS patients. We characterize the immune microenvironment of UPS and its association with oncologic outcomes.
Material and Methods: Surgically resected UPS samples were stained by immunohistochemistry (IHC) for the following: tumor-associated immune cells (CD3, CD8, CD163, CD20), immune checkpoints (stimulatory: OX40, ICOS; inhibitory: PD-L1, LAG3, IDO1, PD1), and the adenosine pathway (CD73, CD39). Sections were reviewed for the presence of lymphoid aggregates (LA). Clinical data were retrospectively obtained for all samples. The Wilcoxon rank-sum and Kruskal-Wallis tests were used to compare distributions. Correlations between biomarkers were measured by Spearman correlation. Univariate and multivariate Cox models were used to identify biomarkers associated with overall survival (OS) and disease-free survival (DFS). Unsupervised clustering was performed, and Kaplan-Meier curves and log-rank tests used for comparison of OS and DFS between immune clusters.
Results: Samples analyzed (n=105) included 46 primary tumors, 34 local recurrences, and 25 metastases. LA were found in 23% (n=10/43), 17% (n=4/24), and 30% (n=7/23) of primary, recurrent, and metastatic samples, respectively. In primary UPS, CD73 expression was significantly higher after preoperative radiation therapy ( p =0.009). CD39 expression was significantly correlated with PD1 expression (primary: p =0.002, recurrent: p =0.004, metastatic: p =0.001), PD-L1 expression (primary: p =0.009), and CD3+ cell densities (primary: p =0.016, recurrent: p =0.043, metastatic: p =0.028). In recurrent tumors, there was a strong correlation between CD39 and CD73 ( p= 0.015), and both were also correlated with CD163+ cell densities (CD39 p= 0.013; CD73 p< 0.001). In multivariate analyses, higher densities of CD3+ and CD8+ cells (Cox Hazard Ratio [HR]=0.33; p =0.010) were independently associated with OS (CD3+, HR=0.19, p <0.001; CD8+, HR= 0.33, p =0.010) and DFS (CD3+, HR=0.34, p =0.018; CD8+, HR=0.34, p = 0.014). Unsupervised clustering of IHC values revealed three immunologically distinct clusters: immune high, intermediate, and low. In primary tumors, these clusters were significantly associated with OS (log-rank p <0.0001) and DFS ( p <0.001).
Conclusion: We identified three immunologically distinct clusters of UPS Associated with OS and DFS. Our data support further investigations of combination anti-PD-1/PD-L1 and adenosine pathway inhibitors in UPS.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Lazcano, Barreto, Salazar, Carapeto, Traweek, Leung, Gite, Mehta, Ingram, Wani, Vu, Parra, Lu, Zhou, Witt, Cope, Thirasastr, Lin, Scally, Conley, Ratan, Livingston, Zarzour, Ludwig, Araujo, Ravi, Patel, Benjamin, Wargo, Wistuba, Somaiah, Roland, Keung, Solis, Wang, Lazar and Nassif.)
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فهرسة مساهمة: Keywords: adenosine pathway; immune checkpoint inhibitors; immune microenvironment; tertiary lymphoid structures; undifferentiated pleomorphic sarcoma
تواريخ الأحداث: Date Created: 20221031 Latest Revision: 20221102
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC9597628
DOI: 10.3389/fonc.2022.1008484
PMID: 36313661
قاعدة البيانات: MEDLINE
الوصف
تدمد:2234-943X
DOI:10.3389/fonc.2022.1008484