Huang Zigao, Li Baojia, Qin Haiquan, Mo Xianwei
Guangxi Clinical Research Center for Colorectal Cancer, Division of Colorectal & Anal Surgery, Guangxi Medical University Cancer Hospital, Nanning, China.
Front Oncol. 2023 Feb 24;13:1006183. doi: 10.3389/fonc.2023.1006183. eCollection 2023.
Tumor-associated macrophages (TAMs) have been used as potential drug targets in preclinical research and clinical trials of various cancers. However, their distribution in Krukenberg tumors (KTs) remains unclear. We investigated the expression and prognostic value of TAMs in patients with gastrointestinal cancer with KTs.
The infiltration of various types of TAMs was detected in surgical tissues of 35 patients with KTs using immunohistochemical staining. The level of infiltration of TAMs in tumor nests (TN), tumor stroma (TS), and invasive margin (IM) areas was evaluated. The Kaplan-Meier method and univariate/multivariate Cox regression risk models were used to analyze the relationship between the degree of TAMs invasion and overall survival (OS) and progression-free survival (PFS).
The distribution of TAMs exhibited spatial heterogeneity between TN, TS, and IM regions in primary tumor (PT) and KT tissues. TAMs infiltrated in the TN had greater prognostic value and were barely influenced by preoperative neoadjuvant therapy, despite similar grades of invasion in PT and KT tissues. Moreover, the number of CD68+ TAMs in TN of KT tissues was an independent risk factor affecting patient OS, whereas tumor resection scope might be an independent risk factor affecting patient PFS.
In view of the close relationship between TAMs, the tumor microenvironment and patient prognosis, targeting TAMs combined with chemotherapy is expected to become a new approach for the treatment of patients with KTs.
肿瘤相关巨噬细胞(TAM)已在各种癌症的临床前研究和临床试验中用作潜在的药物靶点。然而,它们在库肯勃瘤(KT)中的分布仍不清楚。我们研究了TAM在伴有KT的胃肠道癌患者中的表达及预后价值。
采用免疫组织化学染色检测35例KT患者手术组织中各类TAM的浸润情况。评估TAM在肿瘤巢(TN)、肿瘤基质(TS)和浸润边缘(IM)区域的浸润水平。采用Kaplan-Meier法和单因素/多因素Cox回归风险模型分析TAM浸润程度与总生存期(OS)和无进展生存期(PFS)之间的关系。
在原发性肿瘤(PT)和KT组织中,TAM的分布在TN、TS和IM区域之间表现出空间异质性。尽管PT和KT组织中的浸润程度相似,但TN中浸润的TAM具有更大的预后价值,且几乎不受术前新辅助治疗的影响。此外,KT组织TN中CD68+ TAM的数量是影响患者OS的独立危险因素,而肿瘤切除范围可能是影响患者PFS的独立危险因素。
鉴于TAM、肿瘤微环境与患者预后之间的密切关系,靶向TAM联合化疗有望成为治疗KT患者的新方法。