Wustrack Rosanna L, Shao Evans, Sheridan Joey, Zimel Melissa, Cho Soo-Jin, Horvai Andrew E, Luong Diamond, Kwek Serena S, Fong Lawrence, Okimoto Ross A
Department of Orthopedic Surgery, University of California, San Francisco, USA.
Division of Hematology and Oncology, Department of Medicine, University of California, 513 Parnassus Avenue, HSW1201, San Francisco, CA, 94143, USA.
Cancer Immunol Immunother. 2021 Oct;70(10):3031-3040. doi: 10.1007/s00262-021-02935-2. Epub 2021 Apr 17.
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.
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.
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 + PD1 infiltrating T cells in UPS tumors.
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.
软组织肉瘤(STS)是一组罕见的间充质恶性肿瘤,约占成人癌症的1%。未分化多形性肉瘤(UPS)是成人STS最常见的亚型之一。几十年来,UPS患者的临床分层没有进展,仍然依赖于以肿瘤为中心的指标,包括肿瘤大小和深度。我们对肿瘤微环境与这些临床病理参数之间关系的理解仍然有限。
在此,我们对15例新鲜切除的UPS肿瘤进行了基于单细胞流式细胞术的免疫分析,并使用UPS患者的前瞻性和回顾性队列,将该分析与临床、组织病理学和预后数据相结合。
我们发现了UPS肿瘤的生理和解剖特性与肿瘤微环境中免疫细胞组成之间的相关性。具体而言,我们发现肿瘤浸润性CD8 + T细胞与UPS肿瘤大小呈负相关;肿瘤浸润性CD8 + T细胞与总生存期呈正相关。此外,我们证明了解剖位置(深部或浅表)与UPS肿瘤中CD4 + PD1浸润性T细胞频率之间的关联。
我们的研究提供了基于免疫的UPS患者肿瘤微环境分析,并描述了基于肿瘤大小和深度的肿瘤浸润淋巴细胞的不同组成。