Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Front Immunol. 2023 Dec 5;14:1289753. doi: 10.3389/fimmu.2023.1289753. eCollection 2023.
Immunotherapies have formed an entirely new treatment paradigm for hepatocellular carcinoma (HCC). Tertiary lymphoid structure (TLS) has been associated with good response to immunotherapy in most solid tumors. Nonetheless, the role of TLS in human HCC remains controversial, and recent studies suggest that their functional heterogeneity may relate to different locations within the tumor. Exploring factors that influence the formation of TLS in HCC may provide more useful insights. However, factors affecting the presence of TLSs are still unclear. The human gut microbiota can regulate the host immune system and is associated with the efficacy of immunotherapy but, in HCC, whether the gut microbiota is related to the presence of TLS still lacks sufficient evidence.
We performed pathological examinations of tumor and para-tumor tissue sections. Based on the location of TLS in tissues, all patients were divided into intratumoral TLS (It-TLS) group and desertic TLS (De-TLS) group. According to the grouping results, we statistically analyzed the clinical, biological, and pathological features; preoperative gut microbiota data; and postoperative pathological features of patients.
In a retrospective study cohort of 60 cases from a single center, differential microbiota analysis showed that compared with the De-TLS group, the abundance of Lachnoclostridium, Hungatella, Blautia, Fusobacterium, and Clostridium was increased in the It-TLS group. Among them, the enrichment of Lachnoclostridium was the most significant and was unrelated to the clinical, biological, and pathological features of the patients. It can be seen that the difference in abundance levels of microbiota is related to the presence of TLS.
Our findings prove the enrichment of Lachnoclostridium-dominated gut microbiota is associated with the presence of It-TLS in HCC patients.
免疫疗法为肝细胞癌(HCC)形成了全新的治疗模式。在大多数实体瘤中,三级淋巴结构(TLS)与免疫治疗的良好反应相关。然而,TLS 在人 HCC 中的作用仍存在争议,最近的研究表明其功能异质性可能与肿瘤内的不同位置有关。探索影响 HCC 中 TLS 形成的因素可能提供更有用的见解。然而,影响 TLS 存在的因素仍不清楚。人类肠道微生物群可以调节宿主免疫系统,并与免疫治疗的疗效相关,但在 HCC 中,肠道微生物群是否与 TLS 的存在有关仍缺乏足够的证据。
我们对肿瘤和肿瘤旁组织切片进行了病理检查。根据 TLS 在组织中的位置,所有患者被分为肿瘤内 TLS(It-TLS)组和荒漠型 TLS(De-TLS)组。根据分组结果,我们对患者的临床、生物学和病理学特征、术前肠道微生物群数据和术后病理特征进行了统计分析。
在来自单一中心的 60 例回顾性研究队列中,差异微生物组分析显示,与 De-TLS 组相比,It-TLS 组中lachnoclostridium、Hungatella、Blautia、Fusobacterium 和 Clostridium 的丰度增加。其中,lachnoclostridium 的富集最为显著,与患者的临床、生物学和病理学特征无关。可以看出,微生物群的丰度水平差异与 TLS 的存在有关。
我们的研究结果证明了富含lachnoclostridium 的肠道微生物群与 HCC 患者存在 It-TLS 有关。