Targeting Pathogenic Myelopoiesis in Pancreatic Cancer (PaMPa)

August 14, 2026 updated by: Giulio Belfiori, IRCCS San Raffaele

This prospective observational study aims to investigate pathogenic myelopoiesis in patients with pancreatic ductal adenocarcinoma (PDAC) and to characterize the systemic immune alterations associated with tumor-related inflammation.

The study will enroll 50 patients with newly diagnosed, non-metastatic, treatment-naïve PDAC and 50 age-matched control patients with intraductal papillary mucinous neoplasm (IPMN) under surveillance and no evidence of pancreatic malignancy. Control patients will be matched to PDAC patients by age within a range of ±5 years whenever feasible.

A single peripheral blood sample will be collected at baseline from all participants. In PDAC patients, blood collection will be performed before initiation of any anti-tumor treatment. Translational analyses will characterize circulating myeloid cells, progenitor cells, and hematopoietic stem and progenitor cell-related transcriptional programs using high-dimensional flow cytometry and single-cell transcriptomic analyses.

The primary objective is to identify the molecular drivers of pathogenic myelopoiesis in PDAC by assessing quantitative and qualitative differences between PDAC patients and age-matched controls in circulating myeloid and progenitor cell populations and their transcriptional profiles. The study will specifically explore the hypothesis that IL-1β-associated tumor inflammation contributes to systemic reprogramming of hematopoietic progenitor compartments and promotes myeloid-biased hematopoiesis.

PDAC patients will also be followed clinically for 12 months using data derived from routine clinical practice to explore associations between baseline pathogenic myelopoiesis-related profiles and subsequent clinical outcomes. No follow-up is required for control patients.

Study Overview

Status

Not yet recruiting

Conditions

Pancreatic Diseases

Detailed Description

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly inflammatory and immunosuppressive tumor microenvironment. During cancer progression, tumor-derived inflammatory signals can alter hematopoiesis and promote the expansion of myeloid cells with pro-tumorigenic functions. Inflammatory cytokines, including interleukin-1 beta (IL-1β), may act on hematopoietic stem and progenitor cells (HSPCs), inducing genomic and metabolic reprogramming and favoring myeloid-biased hematopoiesis. Previous and preliminary findings suggest that IL-1β may contribute to pathogenic inflammation in PDAC and to systemic conditioning of the immune system. The study hypothesis is that IL-1β-associated tumor inflammation reprograms hematopoietic progenitor compartments, leading to persistent generation of pro-inflammatory myeloid cells that may contribute to PDAC progression and recurrence.

This is a monocentric, prospective observational cohort study designed to characterize pathogenic myelopoiesis in patients with PDAC. The study will include 50 patients with newly diagnosed, non-metastatic, treatment-naïve PDAC and 50 age-matched control patients. Control patients will be recruited among individuals with intraductal papillary mucinous neoplasm (IPMN) under surveillance at the Pancreatic Cystic Lesion outpatient clinic, with no evidence of pancreatic malignancy at enrollment. Controls will be selected to match the age of PDAC patients within a range of ±5 years whenever feasible.

The primary objective is to identify the molecular drivers of pathogenic myelopoiesis in PDAC patients. At baseline, quantitative and qualitative differences between PDAC patients and age-matched controls will be evaluated in the frequency and phenotype of circulating myeloid and progenitor cell populations using high-dimensional flow cytometry. Transcriptional profiles of circulating myeloid cells and HSPCs will also be characterized, including differentially expressed genes, gene ontology annotations, and gene regulatory networks.

After informed consent and verification of eligibility criteria, demographic and relevant clinical data will be collected. All participants will undergo a single peripheral blood collection of approximately 14 mL specifically for research purposes. In PDAC patients, blood will be collected at baseline before initiation of any anti-tumor treatment. Control patients will undergo the same baseline blood sampling for comparator translational analyses. Peripheral blood sampling is the only study-specific procedure; no investigational medicinal products or therapeutic interventions will be administered as part of the study.

Blood samples will undergo translational laboratory analyses aimed at characterizing circulating myeloid cells, progenitor cells, and HSPC-related transcriptional programs. Planned analyses include high-dimensional flow cytometry and transcriptomic and epigenetic analyses. Biological samples will be processed according to established laboratory procedures and used exclusively for the analyses described in the study protocol.

In addition to the human translational component, the research project includes experimental studies aimed at investigating the persistence and molecular determinants of IL-1β-induced reprogramming of bone marrow progenitor cells. In mouse models, the persistence of IL-1β-dependent reprogramming will be evaluated through characterization of circulating and bone marrow myeloid populations, transcriptional profiles, and tumor growth following experimental tumor challenge. Exploratory analyses will investigate transcriptional and epigenetic programs associated with IL-1β-induced inflammatory memory, including differential gene expression, chromatin accessibility, histone modifications, and transcription factor regulatory programs. Candidate mechanisms identified experimentally will be evaluated in relation to IL-1β-dependent signatures detected in circulating monocytes from PDAC patients compared with age-matched controls.

PDAC patients will be followed clinically for 12 months after enrollment. No additional protocol-mandated visits or procedures are required during follow-up. Clinical information will be obtained exclusively from routine standard-of-care visits and medical records and will include, where available, treatments received, disease status, recurrence, progression, and survival. These data will be used to explore associations between baseline pathogenic myelopoiesis-related profiles and subsequent clinical outcomes. Control patients will not undergo study-specific follow-up after baseline assessment.

Statistical analyses will primarily be descriptive and exploratory. Baseline biological features will be compared between PDAC patients and age-matched controls using appropriate parametric or non-parametric statistical methods and bioinformatic approaches for high-dimensional datasets. Associations between baseline biological features and clinical outcomes will also be explored within the PDAC cohort.

The planned enrollment period is 2 years. PDAC patients will participate in clinical follow-up for 12 months, while control patients will undergo baseline assessment only. The overall study duration is expected to be 3 years.

Study Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Giulio Belfiori
Phone Number: 0226437810
Email: belfiori.giulio@hsr.it

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

Adult
Older Adult

Accepts Healthy Volunteers

Sampling Method

Non-Probability Sample

Study Population

The study population will include adults with newly diagnosed, non-metastatic, treatment-naïve pancreatic ductal adenocarcinoma (PDAC) evaluated at the Pancreatic Surgery Unit of IRCCS Ospedale San Raffaele, and age-matched control patients. Controls will be recruited among patients with intraductal papillary mucinous neoplasm (IPMN) under surveillance at the Pancreatic Cystic Lesion outpatient clinic, with no evidence of pancreatic malignancy at enrollment. Control patients will be selected to match the age of PDAC patients within ±5 years whenever feasible. The study will include 50 PDAC patients and 50 age-matched controls

Description

Inclusion Criteria

For all participants:
Age ≥18 years.
Ability and willingness to autonomously provide written informed consent.
For the PDAC cohort:
Clinical diagnosis of non-metastatic pancreatic ductal adenocarcinoma (PDAC).
Treatment-naïve status at the time of blood collection, with no prior chemotherapy, radiotherapy, or immunotherapy for PDAC.
Newly diagnosed non-metastatic pancreatic cancer eligible for multimodal treatment.
Candidate for standard clinical management at IRCCS Ospedale San Raffaele.
For the age-matched control cohort:
Patient followed at the Pancreatic Cystic Lesion outpatient clinic of IRCCS Ospedale San Raffaele.
Diagnosis of intraductal papillary mucinous neoplasm (IPMN) under surveillance, with no evidence of pancreatic malignancy at the time of enrollment.
Age within ±5 years of the corresponding PDAC cohort to allow age-matched comparator analyses.
Exclusion Criteria
For all participants:
Inability to autonomously provide informed consent.
For the PDAC cohort:
Failure to meet the inclusion criteria for the PDAC cohort.
Presence of severe comorbidities that, in the investigator's opinion, may interfere with study participation or interpretation of study results.
Previous systemic anti-cancer treatment for PDAC.
Use of anti-inflammatory drugs, including NSAIDs or immunomodulators.
Events or conditions affecting inflammatory parameters, including acute inflammatory or infectious events such as cholangitis, jaundice, or recent invasive procedures.
Hematologic diseases.
Clinically significant hematological abnormalities that may interfere with immune profiling analyses, as assessed by the investigator.
For the age-matched control cohort:
Any acute or chronic inflammatory condition or ongoing infection.
Any history of cancer or immunological disorders.

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

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
Treatment-naïve PDAC patients Adults with newly diagnosed, non-metastatic pancreatic ductal adenocarcinoma (PDAC), enrolled before initiation of chemotherapy, radiotherapy, or immunotherapy. Participants will undergo a single 14 mL peripheral blood collection at baseline, prior to any anti-tumor treatment, for translational analyses including high-dimensional flow cytometry and single-cell transcriptomic profiling. Clinical follow-up data will be collected from routine clinical practice for 12 months
Age-matched IPMN control patients Adults with intraductal papillary mucinous neoplasm (IPMN) under surveillance and no evidence of pancreatic malignancy at enrollment, selected as age-matched controls for the PDAC cohort (within ±5 years whenever feasible). Participants will undergo a single 14 mL peripheral blood collection at baseline for comparator translational analyses. No study-specific follow-up is required for control participants.

Group / Cohort

Treatment-naïve PDAC patients

Adults with newly diagnosed, non-metastatic pancreatic ductal adenocarcinoma (PDAC), enrolled before initiation of chemotherapy, radiotherapy, or immunotherapy. Participants will undergo a single 14 mL peripheral blood collection at baseline, prior to any anti-tumor treatment, for translational analyses including high-dimensional flow cytometry and single-cell transcriptomic profiling. Clinical follow-up data will be collected from routine clinical practice for 12 months

Age-matched IPMN control patients

Adults with intraductal papillary mucinous neoplasm (IPMN) under surveillance and no evidence of pancreatic malignancy at enrollment, selected as age-matched controls for the PDAC cohort (within ±5 years whenever feasible). Participants will undergo a single 14 mL peripheral blood collection at baseline for comparator translational analyses. No study-specific follow-up is required for control participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and phenotype of circulating myeloid and progenitor cell populations Time Frame: Baseline, prior to initiation of anti-tumor treatment	Quantitative and phenotypic differences in circulating myeloid and progenitor cell populations between treatment-naïve PDAC patients and age-matched control patients, assessed by high-dimensional flow cytometry	Baseline, prior to initiation of anti-tumor treatment
Transcriptional profiles of circulating myeloid cells and hematopoietic stem and progenitor cells Time Frame: Baseline, prior to initiation of anti-tumor treatment	Differences in transcriptional profiles of circulating myeloid cells and hematopoietic stem and progenitor cells (HSPCs) between treatment-naïve PDAC patients and age-matched control patients, including differentially expressed genes, gene ontology annotations, and gene regulatory networks.	Baseline, prior to initiation of anti-tumor treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IL-1β-associated transcriptional signatures in circulating monocytes Time Frame: Baseline, prior to initiation of anti-tumor treatment	Presence and differential expression of IL-1β-associated transcriptional signatures in circulating monocytes from treatment-naïve PDAC patients compared with age-matched control patients, as part of the validation of candidate regulators of IL-1β-induced inflammatory memory	Baseline, prior to initiation of anti-tumor treatment

Collaborators and Investigators

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

Sponsor

IRCCS San Raffaele

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 (Estimated)

September 30, 2026

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2029

Study Registration Dates

First Submitted

August 11, 2026

First Submitted That Met QC Criteria