The Role of Tumor-associated Macrophages in Colorectal Liver Metastases

March 22, 2019 updated by: Matteo Donadon, Humanitas Clinical and Research Center

Search for the Clinical Significance of Tumor-associated Macrophages in Patients With Colorectal Liver Metastases

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Procedure: Hepatectomy

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.

Study Type

Observational

Enrollment (Actual)

101

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients affected by colorectal liver metastases treated by hepatectomy.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival Time Frame: From date of surgery until the date of first documented progression or date of death from any cause, which ever came first assessed up to 72 months]	Analysis of survival after hepatic resection for colorectal liver metastases according with the tumor-associated macrophages characteristics	From date of surgery until the date of first documented progression or date of death from any cause, which ever came first assessed up to 72 months]

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Humanitas Clinical and Research Center

Investigators

Principal Investigator: Matteo Donadon, MD, PhD, Humanitas University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2015

Primary Completion (Actual)

December 31, 2017

Study Completion (Actual)

March 1, 2019

Study Registration Dates

First Submitted

March 21, 2019

First Submitted That Met QC Criteria

March 22, 2019

First Posted (Actual)

March 25, 2019

Study Record Updates

Last Update Posted (Actual)