Anti-inflammatory mechanisms in cancer research: Characterization of a distinct M2-like macrophage model derived from the THP-1 cell line.

AIMS: Macrophages play an essential role in cancer development. Tumor-associated macrophages (TAMs) have predominantly M2-like attributes that are associated with tumor progression and poor patient survival. Numerous methods have been reported for differentiating and polarizing macrophages in vitro, but there is no standardized and validated model for creating TAMs. Primary cells show varying cytokine responses depending on their origin and functional studies utilizing these cells may lack generalization and validity. A distinct cell line-derived TAM-like M2 subtype is required to investigate the mechanisms mediated by anti-inflammatory TAMs in vitro. Our previous work demonstrated a standardized protocol for creating an M2 subtype derived from a human THP-1 cell line. The cell expression profile, however, has not been validated. The aim of this study was to characterize and validate the TAM-like M2 subtype macrophage created based on our protocol to introduce them as a standardized model for cancer research. METHODS AND RESULTS: Using qRT-PCR and ELISA, we demonstrated that proinflammatory, anti-inflammatory, and tumor-associated marker expression changed during THP-1-derived marcrophage development in vitro, mimicking a TAM-related profile (e.g., TNFα, IL-1ß). The anti-inflammatory marker IL-8/CXCL8, however, is most highly expressed in young M0 macrophages. Flow cytometry showed increased expression of CD206 in the final TAM-like M2 macrophage. Single-cell RNA-sequencing analysis of primary human monocytes and colon cancer tissue macrophages demonstrated that cell line-derived M2 macrophages resembled a TAM-related gene profile. CONCLUSIONS: The THP-1-derived M2 macrophage based on a standardized cell line model represents a distinct anti-inflammatory TAM-like phenotype with an M2a subtype profile. This model may provide a basis for in vitro investigation of functional mechanisms in a variety of anti-inflammatory settings, particularly colon cancer development.

Unmet Challenges in Patients with Crohn's Disease.

Patients with Crohn's disease can present with a variety of clinical manifestations; treatment strategies should focus on long-term remission and improvement of quality of life. There is no standardized process of diagnosing, predicting prognosis, and treating the disease. This narrative review was based on a literature search using PubMed, Embase, and Science Direct. Data on unmet challenges in patients with Crohn's disease were extracted from identified manuscripts. The aim was to discuss present research on standardized processes in the management of patients with Crohn's disease and to identify the unmet needs in clinical evaluation and treatment approaches. There is no consensus on standardized diagnostic, treatment, and surveillance algorithms, particularly in assessing complications of Crohn's, such as stricturing disease, intestinal cancer risk, and cutaneous manifestations. Complications and treatment failure rates of conventional, interventional, and surgical therapy place emphasis on the need for standardized treatment algorithms, particularly in the case of acute complications of the disease. Research on standardized clinical approaches, reliable biomarkers for disease diagnosis and therapy monitoring, and new treatment agents is necessary to improve therapy and reduce complications in patients with Crohn's disease.