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

Tumor morphology and location associate with immune cell composition in pleomorphic sarcoma.
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DOI:
10.1007/s00262-021-02935-2
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发表时间:
2021-10
期刊:
Cancer immunology, immunotherapy : CII
影响因子:
--
通讯作者:
Okimoto RA
Okimoto RA
中科院分区:
其他
文献类型:
--
作者:
Wustrack RL;Shao E;Sheridan J;Zimel M;Cho SJ;Horvai AE;Luong D;Kwek SS;Fong L;Okimoto RA

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软组织肉瘤(STS)是一组罕见的间叶恶性肿瘤,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。UPS患者的临床分层几十年来一直没有发展,并继续依赖于肿瘤为中心的指标,包括肿瘤大小和深度。我们对肿瘤微环境如何与这些临床病理参数相关的理解仍然有限。在这里,我们对15例新鲜切除的UPS肿瘤进行了单细胞流式细胞术免疫分析,并使用前瞻性和回顾性UPS患者队列将该分析与临床,组织病理学和结局数据相结合。我们揭示了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,我们确定了肿瘤浸润性CD 8 + T细胞与UPS肿瘤大小之间的负相关性;以及肿瘤浸润性CD 8 + T细胞与总生存率之间的正相关性。此外,我们证明了UPS肿瘤的解剖位置(深部或浅表)与CD 4 + PD 1hi浸润T细胞频率之间的相关性。我们的研究提供了对UPS患者肿瘤微环境的基于免疫的分析,并描述了基于大小和肿瘤深度的肿瘤浸润淋巴细胞的不同组成。在线版本包含补充材料,可通过10.1007/s 00262 -021-02935-2获得。
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 + PD1hi 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. The online version contains supplementary material available at 10.1007/s00262-021-02935-2.
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