Targeting Pathogenic Myelopoiesis in Pancreatic Cancer
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 100
- 主要终点
- Frequency and phenotype of circulating myeloid and progenitor cell populations
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
结局指标
主要结局
Frequency and phenotype of circulating myeloid and progenitor cell populations
时间窗: 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
Transcriptional profiles of circulating myeloid cells and hematopoietic stem and progenitor cells
时间窗: 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.
次要结局
- IL-1β-associated transcriptional signatures in circulating monocytes(Baseline, prior to initiation of anti-tumor treatment)
研究者
Giulio Belfiori
MD Surgeon
IRCCS San Raffaele