PO.TB10.10 · 肿瘤生物学

结直肠癌中的三级淋巴结构：临床意义及其与CAFs和免疫微环境的相互作用

Tertiary lymphoid structures in colorectal cancer: Clinical significance and their interaction with CAFs and the immune microenvironment

编号 2218 展板 4 时间 4/20 09:00–12:00 区域 Section 31 主讲 Zizhou Wang, BS

分会场 Tertiary Lymphoid Structures in Cancer

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作者与单位 Authors & Affiliations

Zizhou Wang¹, Hiroaki Kasashima¹, Yukina Kusunoki², Yasuhiro Fukui¹, Iguru Omori¹, Nobuhiro Naito¹, Hideki Tanda¹, Yuki Seki¹, Kenji Kuroda¹, Yuichiro Miki¹, Mami Yoshii¹, Tatsuro Tamura¹, Masatsune Shibutani¹, Takahiro Toyokawa¹, Yu Muta³, Yuki Nakanishi³, Masakazu Yashiro⁴, Kiyoshi Maeda¹

¹Department of Gastroenterological Surgery, Osaka Metropolitan University, Osaka, Japan,²Department of Pathophysiology, Osaka Metropolitan University, Osaka, Japan,³Department of Gastroenterology and Hepatology, Kyoto University, Japan, Kyoto, Japan,⁴Department of Molecular Oncology and Therapeutics, Osaka Metropolitan University, Osaka, Japan

摘要 Abstract

中文摘要

结直肠癌(CRC)是一种全球死亡率高的主要恶性肿瘤。肿瘤免疫微环境，特别是三级淋巴结构(TLSs)，因其在抗肿瘤免疫中的作用而日益受到关注。然而，它们在CRC中的具体功能以及TLS相关细胞的预后相关性仍不明确。我们分析了166例接受根治性切除的CRC患者，通过苏木精-伊红(H&E)染色和CD20、alpha-SMA、CD8、CD4及CD103的免疫组化评估TLS。我们还使用双重面板(CD20和alpha-SMA)进行了基于Opal的多重免疫荧光(mIF)，以验证TLS内癌相关成纤维细胞(CAFs)的存在。患者按TLS密度和免疫细胞浸润水平进行分类。TLS主要位于浸润边缘，较高的TLS密度与更好的预后相关(P < 0.05)。相反，TLS内高CAF密度与较差的结局相关(P < 0.01)，而CD8⁺ T细胞的高丰度预示着生存改善。此外，使用Xenium Explorer空间转录组学，我们确认了结直肠癌TLS内CAFs和免疫细胞的空间共存。特别是，TLS内CAF的积累可能重塑免疫微环境，并可能损害抗肿瘤T细胞活性。

查看英文原文 English abstract

Colorectal cancer (CRC) is a major malignancy with high global mortality. The tumor immune microenvironment, particularly tertiary lymphoid structures (TLSs), has gained increasing attention for its role in antitumor immunity. However, their specific functions in CRC and the prognostic relevance of TLS-associated cells remain unclear. We analyzed 166 CRC patients who underwent curative resection, evaluating TLSs by hematoxylin and eosin (H&E) staining and immunohistochemistry for CD20, alpha-SMA, CD8, CD4 and CD103. We additionally performed Opal-based multiplex immunofluorescence (mIF) with a two-plex panel (CD20 and alpha-SMA) to validate the presence of cancer-associated fibroblasts (CAFs) within TLSs. Patients were categorized by TLS density and immune-cell infiltration levels. TLSs were predominantly located at invasive margins, and higher TLS density correlated with better prognosis (P < 0.05). In contrast, high CAF density within TLSs was associated with poorer outcomes (P < 0.01), whereas a high abundance of CD8⁺ T cells predicted improved survival. Furthermore, using Xenium Explorer spatial transcriptomics, we confirmed the spatial coexistence of CAFs and immune cells within TLSs in colorectal cancer. In particular, CAF accumulation within TLSs may reshape the immune microenvironment and potentially impair antitumor T-cell activity.

利益披露 Disclosure

Z. Wang, None.. H. Kasashima, None.. Y. Kusunoki, None.. Y. Fukui, None.. I. Omori, None.. N. Naito, None.. H. Tanda, None.. Y. Seki, None.. K. Kuroda, None.. Y. Miki, None.. M. Yoshii, None.. T. Tamura, None.. M. Shibutani, None.. T. Toyokawa, None.. Y. Muta, None.. Y. Nakanishi, None.. M. Yashiro, None.. K. Maeda, None.

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