PFKFB3 overexpression in monocytes of patients with colon but not rectal cancer programs pro-tumor macrophages and is indicative for higher risk of tumor relapse [GeoMx]

Circulating monocytes are main source for tumor-associated macrophages (TAMs) that control tumor growth, angiogenesis, metastasis and therapy resistance. We raised the questions how monocyte programming is affected by growing tumors localized in colon and rectal sections, and how treatment onsets affect monocyte programming in the circulation. Patients with rectal cancer and colon cancer were enrolled in the study. Spatial transcriptomic analysis was applied using GeoMX DSP-NGS. The key transcriptional difference between monocytes of patients with colon and rectal cancer was increased expression of PFKFB3, activator of glycolysis that is currently considered as therapy target for major solid cancers. PFKFB3-expressing monocyte-derived macrophages massively infiltrated tumor in colon. Nanostring technology identified correlation of PFKFB3 with amount and tumor-promoting properties of TAMs in colon but not in rectal cancer. The study included patients with colorectal adenocarcinoma with morphologically verified diagnosis, treated in the Department of abdominal oncology, Cancer Research Institute of Tomsk National Research Medical Center (Tomsk, Russia). The study was carried out according to Declaration of Helsinki (from 1964, revised in 1975 and 1983) and was approved by the local committee of Medical Ethics of Tomsk Cancer Research Institute (15 May 2019, the approval No. 6/1); all patients signed informed consent for the study. FFPE samples (5 μm) were taken from 5 untreated patients with colon cancer and 5 NAC-treated patients with rectal cancer to perform spatially resolved RNA profiling via NanoString GeoMx digital spatial profiling (DSP). We used the Cancer Transcriptome Atlas (CTA) panel designed for comprehensive profiling of tumor biology, the tumor microenvironment, and the immune response