The Role of Tumor-associated Macrophages in Colorectal Liver Metastases

NCT ID: NCT03888638

Last Updated: 2019-03-25

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 101 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-01-01
• Study Completion Date: 2019-03-01

Brief Summary

Colorectal cancer is a major cause of mortality worldwide. Most patients develop colorectal liver metastases (CLM), and for such patients hepatectomy combined with chemotherapy may be curative. Nevertheless, in the era of precision medicine there is a critical need of prognostic markers to cope with the heterogeneity of CLM patients. Tumor-associated macrophages (TAMs) pave the way to tissue invasion and intravasation providing a nurturing microenvironment formetastases. The quantification of immune landscape of tumors has provided novel prognostic indicators of cancer progression, and the quantification of TAMs might explain the heterogeneity of CLM patients. Here, we will investigate the development of a new diagnostic tool based on TAMs with the aim to define the causative role of TAMs in CLM patients. This will open new clinical scenarios both for the diagnosis, therapy and prognosis, leading to the refinement of the therapeutic output in a personalized medicine perspective.

Detailed Description

Some preliminary data produced by the research team from Humanitas Clinical and Research Center in Milan (ITALY) have shown that TAMs in CLM are heterogeneous and that their diversity can be distinguished based on their morphology and functionality. Therefore, TAMs may represent an additional tool in the definition of the biology and prognosis of CLM patients. This preliminary finding provides us with the rationale to undertake a prospective study on a large series of CLM patients surgically resected by our unit aimed at validating the promisingcorrelation between different TAMs phenotypes and patients prognosis. The characterization of the diversity of TAMs in CLM will be refined using state of the art technology, including multi-parametric flow cytometry, single cell RNA sequencing (scRNA-seq) transcriptional profiling, metabolomic, and proteomic analyses. The expected findings will allow us to develop a new diagnostic tool based on TAMs features, which will open the way to new criteria for patient stratification and for the design of new targeted therapies in a personalized medicine perspective.

Conditions

Colorectal Liver Metastases; Colorectal Cancer; Liver Metastases; Immunotherapy

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Interventions

Hepatectomy

Removal of a part of the liver because of tumor

Intervention Type: PROCEDURE

Other Intervention Names

Liver resection

Eligibility Criteria

Inclusion Criteria

• Patients with colorectal liver metastases undergoing hepatectomy
• Full clinical, surgical, pathological and follow-up data
• Availability of tissues for the analysis

Exclusion Criteria

• Missing (any) data
• Combination of radiofrequency or microwave ablation plus surgery

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Humanitas Clinical and Research Center

OTHER

Sponsor Role: lead

Responsible Party

Matteo Donadon

Assistant Professor of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Matteo Donadon, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Humanitas University

References

Costa G, Sposito C, Soldani C, Polidoro MA, Franceschini B, Marchesi F, Nasir FD, Virdis M, Vingiani A, Leo A, Di Tommaso L, Kotha S, Mantovani A, Mazzaferro V, Donadon M, Torzilli G. Macrophage morphology and distribution are strong predictors of prognosis in resected colorectal liver metastases: results from an external retrospective observational study. Int J Surg. 2023 May 1;109(5):1311-1317. doi: 10.1097/JS9.0000000000000374.

Reference Type: DERIVED

PMID: 37037585 (View on PubMed)

Other Identifiers

TAMs in CLM

Identifier Type: -

Identifier Source: org_study_id