A Master Regulator of Lipid-Associated Macrophage Function in Cancer

NCT07848061 | Not Yet Recruiting

• 1 other identifier: 27073
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Cancer progression is shaped not only by genetic alterations but also by systemic and local metabolic changes that influence the tumor microenvironment (TME). In particular, dysregulated lipid metabolism and micronutrient availability can modulate immune cell function and favor the accumulation of immunosuppressive myeloid populations associated with tumor growth, immune evasion, and poor clinical outcome. Among tumor-infiltrating myeloid cells, macrophages show high metabolic plasticity and adapt their phenotype in response to environmental cues. A subset of macrophages characterized by intracellular lipid accumulation and expression of lipid metabolism-related genes, known as lipid-associated macrophages (LAMs), has been identified in metabolic disorders and, more recently, in several solid tumors, including breast, prostate, and head and neck cancers. In cancer, LAMs are generally associated with immunosuppressive functions, impaired anti-tumor immunity, extracellular matrix remodeling, tumor cell survival, and unfavorable prognosis. Their accumulation may reflect both local metabolic alterations within the TME and systemic metabolic dysregulation, such as obesity and altered lipid homeostasis. However, the factors regulating LAM differentiation and function in human cancers remain poorly defined. Folate is an essential micronutrient involved in DNA synthesis, repair, methylation, and cellular metabolism. Folate deficiency is frequently observed in metabolic disorders, including obesity, and has also been reported in patients with advanced malignancies. Although epidemiological studies have linked folate status to cancer risk, progression, and mortality, results vary across tumor types and populations. Emerging evidence suggests that folate availability may influence lipid metabolism and immune cell differentiation, potentially affecting macrophage polarization within tumors. Experimental studies indicate that folate depletion can alter fatty acid metabolism and promote lipid accumulation in different cell types. Moreover, folate uptake by macrophages is polarization-dependent, and folate receptor beta is selectively expressed by M2-like, immunosuppressive tumor-associated macrophages, supporting a possible link between folate metabolism and macrophage phenotype. Altered folate metabolism may therefore contribute to macrophage metabolic reprogramming toward lipid-associated and immunosuppressive states in the TME. Since diet and micronutrient availability are increasingly recognized as modulators of anti-cancer immune responses, understanding the relationship between folate status, lipid metabolism, and LAMs in cancer patients may provide relevant mechanistic and prognostic insights. Given the limited human data available, an observational study using biological samples collected during routine clinical care represents an appropriate approach to investigate these associations without exposing participants to additional risks.

Conditions

Breast Cancer; Head & Neck Cancer

Outcome Measures

Primary Outcomes (1)

• Association between folate levels and lipid metabolic alterations

  To investigate the association between folate levels and lipid metabolic alterations in immune cells, specifically on macrophages, and biological samples obtained from both head and neck and breast cancer patients.

  5 years

Secondary Outcomes (2)

• Immune cell phenotypes/macrophagesand folate status

  5 years

• Clinical features and folate/lipid metabolism

  5 years

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients diagnosed with solid tumors who are undergoing standard diagnostic or therapeutic procedures. In details, cancer patients affected by Head and Neck Squamous Cell Carcinoma and Brest cancer, who underwent surgical resection at the Policlinic Agostino Gemelli (Fondazione Policlinico Universitario "Agostino Gemelli". - I.R.C.C.S.).

You may qualify if:

• Adult cancer patients with ≥ 18 years.
• Patients who will agree to take part to the study and signed informed consent.
• Availability of clinicopathological record.
• Patients diagnosed by Head and Neck Squamous Cell Carcinoma that underwent surgery.
• Patients diagnosed by and Brest cancer that underwent surgery.

You may not qualify if:

• Inability or unwillingness to provide informed consent.
• Patients with ≤18 years.
• Incomplete clinical data.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Universitario A. Gemelli IRCCS

Roma, 00168, Italy

Location

MeSH Terms

Conditions

Breast Neoplasms; Head and Neck Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Gianluca Franceschini

  Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gianluca Franceschini

CONTACT

+39 0630151; gianluca.franceschini@policlinicogemelli.it

Eleonora Timperi

CONTACT

eleonora.timperi@unicatt.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2026
• First Posted: September 29, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 1, 2031
• Study Completion (Estimated): March 31, 2032
• Last Updated: September 29, 2026

Record last verified: 2026-09

Locations

IT (1)