Invasion characteristics and clinical significance of tumor-associated macrophages in gastrointestinal Krukenberg tumors

Abstract

BackgroundTumor-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.MethodsThe 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).ResultsThe 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.ConclusionsIn 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.

Colorectal Origin: A Marker of Favorable Outcome in Krukenberg Tumor? Results from Clinical and Prognostic Analysis

“…Newer treatment regimens and targeted therapy are being tested, and they will undoubtedly affect survival in the future. [23][24][25] OS time is influenced by the site of origin of the primary tumor which was also noted in our study.…”

Macrophage heterogeneity and its interactions with stromal cells in tumour microenvironment

“…In another study, M1 and M2 macrophages were classified into seven predominant subgroups according to CD68, CD163, and CD206, in which the CD68 + CD163 + TAMs localized in both the tumour nest and stroma, and a higher effective density of this subset in the tumour core correlated with better overall survival and relapse-free survival [ 78 ]. Analogously, Huang et al investigated the spatial heterogeneity of TAMs in gastrointestinal Krukenberg tumours and unveiled that patients with high levels of infiltration of CD68 + TAMs and CD11c + TAMs in the tumour nest of primary tumour tissues, instead of CD163 + TAMs, had worse overall survival and progression-free survival, and the infiltration level of CD68 + TAMs in the tumour nest of Krukrnberg tumours was related to overall survival as well, indicating the prognostic value of TAMs in the tumour nest [ 79 ]. Interestingly, contrary clinical outcomes could be associated with the same macrophage subset.…”

Krukenberg Tumour in a 34-Year-Old Female: A Case Report

“…A review of earlier research indicates that gastric cancer (GC) was the primary cause of Krukenberg tumors, with colorectal cancer (CRC), appendix mucinous adenocarcinoma, and breast, prostate, and cervical cancer. It has been proposed that the incidence of CRC associated with the Krukenberg tumor has progressively increased in recent years, surpassing that of the giant cell tumor (GCT) with the Krukenberg tumor [5]. Before, any ovarian cancer that spread to other areas was called a Krukenberg tumor.…”