BACKGROUND: Soft tissue sarcomas (STS) are generally considered non-immunogenic, although specific subtypes respond to immunotherapy. Antitumour response within the tumour microenvironment relies on a balance between inhibitory and activating signals for tumour-infiltrating lymphocytes (TILs). This study analysed TILs and immune checkpoint molecules in STS, and assessed their prognostic impact regarding local recurrence (LR), distant metastasis (DM), and overall survival (OS). METHODS: One-hundred and ninety-two surgically treated STS patients (median age: 63.5 years; 103 males [53.6%]) were retrospectively included. Tissue microarrays were constructed, immunohistochemistry for PD-1, PD-L1, FOXP3, CD3, CD4, and CD8 performed, and staining assessed with multispectral imaging. TIL phenotype abundance and immune checkpoint markers were correlated with clinical and outcome parameters (LR, DM, and OS). RESULTS: Significant differences between histology and all immune checkpoint markers except for FOXP3+ and CD3-PD-L1+ cell subpopulations were found. Higher levels of PD-L1, PD-1, and any TIL phenotype were found in myxofibrosarcoma as compared to leiomyosarcoma (all p < 0.05). The presence of regulatory T cells (Tregs) was associated with increased LR risk (p = 0.006), irrespective of margins. Other TILs or immune checkpoint markers had no significant impact on outcome parameters. CONCLUSIONS: TIL and immune checkpoint marker levels are most abundant in myxofibrosarcoma. High Treg levels are independently associated with increased LR risk, irrespective of margins.
BACKGROUND: Soft tissue sarcomas (STS) are generally considered non-immunogenic, although specific subtypes respond to immunotherapy. Antitumour response within the tumour microenvironment relies on a balance between inhibitory and activating signals for tumour-infiltrating lymphocytes (TILs). This study analysed TILs and immune checkpoint molecules in STS, and assessed their prognostic impact regarding local recurrence (LR), distant metastasis (DM), and overall survival (OS). METHODS: One-hundred and ninety-two surgically treated STS patients (median age: 63.5 years; 103 males [53.6%]) were retrospectively included. Tissue microarrays were constructed, immunohistochemistry for PD-1, PD-L1, FOXP3, CD3, CD4, and CD8 performed, and staining assessed with multispectral imaging. TIL phenotype abundance and immune checkpoint markers were correlated with clinical and outcome parameters (LR, DM, and OS). RESULTS: Significant differences between histology and all immune checkpoint markers except for FOXP3+ and CD3-PD-L1+ cell subpopulations were found. Higher levels of PD-L1, PD-1, and any TIL phenotype were found in myxofibrosarcoma as compared to leiomyosarcoma (all p < 0.05). The presence of regulatory T cells (Tregs) was associated with increased LR risk (p = 0.006), irrespective of margins. Other TILs or immune checkpoint markers had no significant impact on outcome parameters. CONCLUSIONS: TIL and immune checkpoint marker levels are most abundant in myxofibrosarcoma. High Treg levels are independently associated with increased LR risk, irrespective of margins.
Authors: Sandra P D'Angelo; Michelle R Mahoney; Brian A Van Tine; James Atkins; Mohammed M Milhem; Balkrishna N Jahagirdar; Cristina R Antonescu; Elise Horvath; William D Tap; Gary K Schwartz; Howard Streicher Journal: Lancet Oncol Date: 2018-01-19 Impact factor: 41.316
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Authors: Sveinung W Sorbye; Thomas Kilvaer; Andrej Valkov; Tom Donnem; Eivind Smeland; Khalid Al-Shibli; Roy M Bremnes; Lill-Tove Busund Journal: PLoS One Date: 2011-01-27 Impact factor: 3.240
Authors: Jung Ryul Kim; Young Jae Moon; Keun Sang Kwon; Jun Sang Bae; Sajeev Wagle; Kyoung Min Kim; Ho Sung Park; Ho Lee; Woo Sung Moon; Myoung Ja Chung; Myoung Jae Kang; Kyu Yun Jang Journal: PLoS One Date: 2013-12-11 Impact factor: 3.240
Authors: Rawad Elias; Anita Giobbie-Hurder; Nadine Jackson McCleary; Patrick Ott; F Stephen Hodi; Osama Rahma Journal: J Immunother Cancer Date: 2018-04-04 Impact factor: 13.751