Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Department of General Surgery, Huashan Hospital Fudan University, Shanghai, China.
J Immunother Cancer. 2023 Feb;11(2). doi: 10.1136/jitc-2022-006425.
Tertiary lymphoid structures (TLSs) have been proposed to assess the prognosis of patients with cancer. Here, we investigated the prognostic value and relevant mechanisms of TLSs in colorectal cancer liver metastases (CRCLM).
603 patients with CRCLM treated by surgical resection from three cancer centers were included. The TLSs were categorized according to their anatomic subregions and quantified, and a TLS scoring system was established for intratumor region (T score) and peritumor region (P score). Differences in relapse-free survival (RFS) and overall survival (OS) between groups were determined. Multiplex immunohistochemical staining (mIHC) was used to determine the cellular composition of TLSs in 40 CRCLM patients.
T score positively correlated with superior prognosis, while P score negatively associated with poor survival (all p<0.05). Meanwhile, T score was positively associated with specific mutation subtype of KRAS. Furthermore, TLSs enrichment gene expression was significantly associated with survival and transcriptomic subtypes of CRCLM. Subsequently, mIHC showed that the densities of Treg cells, M2 macrophages and Tfh cells were significantly higher in intratumor TLSs than in peritumor TLSs (p0.029, p0.047 and p0.041, respectively), and the frequencies of Treg cells and M2 macrophages were positively correlated with P score, while the frequencies of Tfh cells were positively associated with T scores in intratumor TLSs (all p<0.05). Next, based on the distribution and abundance of TLSs, an Immune Score combining T score and P score was established which categorized CRCLM patients into four immune classes with different prognosis (all p<0.05). Among them, patients with higher immune class have more favorable prognoses. The C-index of Immune Class for RFS and OS was higher than Clinical Risk Score statistically. These results were also confirmed by the other two validation cohorts.
The distribution and abundance of TLSs is significantly associated with RFS and OS of CRCLM patients, and a novel immune class was proposed for predicting the prognosis of CRCLM patients.
三级淋巴结构（TLS）被提出用于评估癌症患者的预后。在这里，我们研究了 TLS 在结直肠癌肝转移（CRCLM）中的预后价值和相关机制。
纳入了来自三个癌症中心的 603 名接受手术切除治疗的 CRCLM 患者。根据其解剖亚区对 TLS 进行分类和定量，并建立了肿瘤内区域（T 评分）和肿瘤周围区域（P 评分）的 TLS 评分系统。比较各组之间无复发生存（RFS）和总生存（OS）的差异。对 40 例 CRCLM 患者进行了多重免疫组化染色（mIHC），以确定 TLS 的细胞组成。
T 评分与较好的预后呈正相关，而 P 评分与不良预后呈负相关（均 p<0.05）。同时，T 评分与 KRAS 特定突变亚型呈正相关。此外，TLS 富集基因表达与 CRCLM 的生存和转录组亚型显著相关。随后，mIHC 显示，肿瘤内 TLS 中的 Treg 细胞、M2 巨噬细胞和 Tfh 细胞的密度明显高于肿瘤周围 TLS（p0.029、p0.047 和 p0.041，分别），Treg 细胞和 M2 巨噬细胞的频率与 P 评分呈正相关，而肿瘤内 TLS 中的 Tfh 细胞频率与 T 评分呈正相关（均 p<0.05）。接下来，根据 TLS 的分布和丰度，建立了一个结合 T 评分和 P 评分的免疫评分，将 CRCLM 患者分为具有不同预后的四个免疫组（均 p<0.05）。其中，免疫等级较高的患者预后较好。免疫等级对 RFS 和 OS 的 C 指数在统计学上高于临床风险评分。这些结果也在另外两个验证队列中得到了验证。
TLS 的分布和丰度与 CRCLM 患者的 RFS 和 OS 显著相关，提出了一种新的免疫组，用于预测 CRCLM 患者的预后。
