Biomarkers for modeling of cancer-specifc tumor-associated macrophages ex vivo

Abstract

Introduction. Tumor-associated macrophages (TAMs) are essential innate immune cells in the tumor microenvironment. TAMs can stimulate cancer cell proliferation and primary tumor growth, angiogenesis, lymphangiogenesis, cancer cell invasiveness in vessels and metastatic niche formation as well as support chemotherapy resistance. TAMs are phenotypically diverse both in various cancer localizations and in intratumoral heterogeneous compartments. Tumor-specific modeling of TAMs is necessary to understand the fundamental mechanism of pro- and anti-tumor activity, to test their interaction with existing therapies, and to develop TAM- targeted immunotherapy. Aim of study: To investigate cancer-specific transcriptomic features of ex vivo human TAM models. Material and Methods. Here we compared transcriptomic profiles of TAMs for breast, colorectal, ovarian, lung, and prostate cancers ex vivo. Human monocytes were isolated from buffy coats, and then stimulated by the tumor cell conditioned medium ex vivo. Using real-time PCR, we quantified the expression of key TAM biomarkers including inflammatory cytokines, scavenger-receptors, angiogenesis-regulating genes, and matrix remodeling factors. Results. PCR analysis allowed revealing cancer-specific expression profiles of modeled TAMs. By comparing the existing knowledge about TAM phenotypes in human tumors in vivo with the collected data, we discuss the advantages and limitation of ex vivo TAM models derived from human blood monocytes. Conclusion. Monocytes-derived macrophages stimulated with cancer cell-conditioned medium can, to a certain extent, allow modeling of cancer-specific programming of TAMs. Our model system is valuable to examine agents reprogramming key TAM pro-tumoral activities, and for the reproducible analysis of mechanistic events that program tolerogenic status of TAMs towards cancer cells.

Keywords

• tumor-associated macrophages
• m1/m2 classification
• cytokines
• scavenger-receptors