(AR P2) Cellular Immunoprofile of Peritoneal Environment during HIPEC Procedure

Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CS-HIPEC) may alter peritoneal immunology and modify tumor-host interaction. We characterized the peritoneal immune cellular profile among CS-HIPEC patients.

Methods: We performed prospective flow cytometric analysis of peritoneal fluid among 15 patients undergoing CS-HIPEC (NCT03230240). Samples were collected at laparotomy and during HIPEC at 0, 30, 60 and 90 minutes for CD34 (stem cells), CD15 (granulocytes), CD14 (monocytes), CD3 (T-lymphocytes), CD3-CD8+ (NK cells), and CD20 (B-lymphocytes).

Results: Mean PCI score was 19.911.5 (median 19) with mean ascites volume 20633183 ml (250). 12 patients had cytoreduction score (CCR) 0/1 and 3 patients had CCR≥2 (20%). There was a single 90-day mortality due to rapid hyper-progression (rhabdomatoid mesothelioma). The proportion of peritoneal NK cells remained stable (p=0.861) throughout perfusion, but significantly evolved for CD4/CD8 ratio (0.850.18, 1.781.10, 2.07 1.34, 2.151.52, 2.221.47, p=0.047), granulocyte/lymphocyte ratio (2.421.80, 49.857.0, 78103.1, 71.6100.1, 140.5263.0, p=0.046), and monocyte/lymphocyte ratio (0.460.35, 1.441.56, 1.821.45, 1.991.40, 2.942.64, p=0.005). Moreover, two distinct patterns of CD4/CD8 T-lymphocytes became evident over time, distinguished by dichotomization at median CD4/CD8 to “high” and “low” groups. Patients maintained their high versus low CD4/CD8 group status over HIPEC time but no association was identified with age (p=0.462), sex (p=1.000), CCR status (p=0.522), complication (p=0.282) or severe complication (p=0.505) occurrence, PCI score (p=0.358) cytoreduction duration (p=0.257) or ascites volume (p=0.713).

Conclusion: Substantial patient-to-patient variability of peritoneal immune response to HIPEC exists. Two distinct immuno-groups emerge based on CD4/CD8 ratio in peritoneal perfusate. The clinical significance of this marked segregation remains elusive while long-term outcomes are pending.