Immunomonitoring of Circulating Immune Cells in Maxillofacial Surgery

Head and Neck Cancer (H&N), Osteoradionecrosis of Jaws, Trauma Sequelae

Immunomonitoring of Circulating Immune, Cells Following Free Flap Reconstruction in Maxillofacial Surgery

The immune response following facial reconstruction may help predict healing time and the date of discharge after maxillofacial surgery. Regulatory T cells (Tregs) are emerging as powerful modulators of the immune response in various contexts during reconstruction. Indeed, Tregs are involved in tissue regeneration, control the local inflammatory response, and promote effective tissue repair while limiting fibrosis. An early increase in circulating Tregs could serve as an indicator of a favorable reparative/regenerative response. Primary objective: To identify changes in the proportion of regulatory T cells (Tregs) among circulating immune cells between the preoperative and postoperative periods, and to assess its association with length of hospital stay. Primary outcome measure: proportion of regulatory T cells (Tregs) among CD4 lymphocytes, measured by flow cytometry at different time points (preoperative, perioperative, and postoperative), and its association with length of hospital stay (days). Study Design: monocentric, including a maximum of 60 patients; Inclusion criteria: Age ≥ 18 years; managed in the department of maxillofacial surgery (Pitié-Salpêtrière Hospital); Scheduled for surgery as part of treatment involving free flap reconstruction; Informed about the study, with no objections, and having provided written consent for genetic testing Exclusion criteria: Pregnant or breastfeeding women; Individuals under legal protective measures Research Process: After verifying eligibility criteria, patients will be informed about the study during a clinical visit. Following a reflection period that the patient deems necessary to make a decision, their lack of objection and consent to genetic testing will be obtained. As part of the research, a 7 mL tube of ACD blood will be collected in addition to the routine blood samples during routine blood draws at the following visits: preoperative, perioperative (during surgery), and postoperative follow-ups (Day 2, Day 5, and Day 15). These tubes will then be analyzed in the Immunology Research Laboratory of Prof. Miyara and Dr. Bouaoud (CIMI, Pitié Salpêtrière) using flow cytometry (counting/assay of Tregs and subpopulations). During the operation, surgical waste (bone, muscle, drainage fluids) will also be collected for research purposes; it will be analyzed in the immunology research laboratory of Prof. Miyara and Dr. Bouaoud (CIMI, Pitié Salpêtrière) using flow cytometry and, in some cases, single-cell transcriptomics when the sample meets the necessary quality criteria (sufficient cell count, viability, etc.).

Description of Knowledge in the Relevant Field: The immune response contributes to tissue repair processes following surgery. Regulatory T cells (Tregs) modulate inflammation and may play a role in enhancing postoperative repair. In particular, Tregs are emerging as powerful modulators of the immune response in various contexts during reconstruction. Indeed, Tregs are involved in tissue regeneration, control the local inflammatory response, and promote effective tissue repair while limiting fibrosis. This study aims to document variations in Treg levels in peripheral blood following reconstructive maxillofacial surgery using free flaps. Description of the Study Population and Rationale for Its Selection: The study population consists of patients undergoing maxillofacial surgery for free-flap reconstruction as part of their treatment, from whom relevant clinical data (healing time, length of hospital stays) can be collected. This selection allows for the exploration of the association between circulating immunological parameters and postoperative outcomes. Description of the research focuses: The research focuses primarily on the quantification and characterization of circulating Tregs (CD4+ CD25+ FOXP3+) and their subpopulations, as well as other cellular compartments of the immune response. Analyses may also be performed on surgical waste (bone, muscle, drainage fluids) if it can be recovered for research purposes, using flow cytometry and, where appropriate, single-cell transcriptomics. These analyses will help establish the immunological profile of tissue-resident Tregs and compare it to that of circulating Tregs. Justification of the study duration: The total planned duration is 8 months, consisting of a recruitment period (6 months) to enroll a sufficient number of participants to analyze the associations between immunological parameters and clinical criteria (length of hospital stay, wound healing), as well as the patient follow-up period (2 months). Primary Outcome Measure: Proportion of regulatory T cells (Tregs) among CD4 lymphocytes, measured by flow cytometry at different time points (preoperative, perioperative, and postoperative), and association with length of hospital stay (days). Secondary Outcome Measures: Kinetics of the increase in circulating Tregs over the course of blood draws (preoperative visit, perioperative period, postoperative follow-up during hospitalization). Associated clinical criteria: time to healing/closure of the surgical wound and time until the decision to discharge the patient from the hospital. Risks and safety monitoring: Non-interventional research is considered to pose no specific research-related risks. In this study, samples are collected during routine blood draws for clinical care, with the addition of a tube designated for analysis. The management of adverse events is governed by the safety monitoring procedures in effect within the context of clinical care. Non-interventional research involving human subjects poses no risk to patients. Adverse events observed in patients participating in the research are reported by the investigators in accordance with local safety monitoring protocols established as part of routine clinical care. Data management Clinical data (age, sex, history of malnutrition, history of immunosuppression, history of systemic anticancer treatment, length of hospitalization, wound healing/closure, discharge decision) are collected by maxillofacial surgeons based on medical observations during hospitalization. Biological data (flow cytometry, any transcriptomic analyses) are collected by biologists in the immunology laboratory. Clinical and biological data, rendered non identifiable, will be recorded in a REDCap® type electronic data collection form (E-CRF) made available free of charge by APHP.

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