Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Jun 24, 2020; 11(6): 397-404
Published online Jun 24, 2020. doi: 10.5306/wjco.v11.i6.397
Immune response activation following hyperthermic intraperitoneal chemotherapy for peritoneal metastases: A pilot study
Giammaria Fiorentini, Donatella Sarti, Alberto Patriti, Emilio Eugeni, Francesco Guerra, Francesco Masedu, Andrew Reay Mackay, Stefano Guadagni
Giammaria Fiorentini, Donatella Sarti, Department of Onco-Hematology, Azienda Ospedaliera “Ospedali Riuniti Marche Nord”, Pesaro 61122, Italy
Alberto Patriti, Emilio Eugeni, Francesco Guerra, Department of General Surgery, Azienda Ospedaliera “Ospedali Riuniti Marche Nord”, Pesaro 61122, Italy
Francesco Masedu, Andrew Reay Mackay, Stefano Guadagni, Department of Applied Clinical Sciences and Biotechnology, University of L’Aquila, L’Aquila 67100, Italy
Author contributions: Fiorentini G was the guarantor and designed the study; Patriti A, Eugeni E, Guerra F performed the procedures and collected the data; Guadagni S and Sarti D participated in the acquisition, analysis, and interpretation of the data, and drafted the initial manuscript; Masedu F and Mackay AR revised the article critically for important intellectual content, statistical analysis and language revision.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of L’Aquila and Teramo (Italy).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Giammaria Fiorentini, MD, Adjunct Professor, Chief Doctor, Director, Department of Onco-Hematology, Azienda Ospedaliera “Ospedali Riuniti Marche Nord”, Via Lombroso 1, Pesaro 61122, Italy. g.fiorentini@alice.it
Received: December 24, 2019
Peer-review started: December 24, 2019
First decision: February 20, 2020
Revised: April 13, 2020
Accepted: May 12, 2020
Article in press: May 12, 2020
Published online: June 24, 2020
Processing time: 181 Days and 14.3 Hours
ARTICLE HIGHLIGHTS
Research background

According to current Network NCCN Guidelines, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is considered the standard treatment for pseudomyxoma peritonei and peritoneal mesothelioma. In several clinical trials, HIPEC, in particular, resulted in survival improvements.

Research motivation

Thermal tumor ablation has been reported to induce a potential immunomodulatory effect, illustrated by the intense inflammatory cell response, including: Dendritic cells, neutrophils, macrophages, B and T lymphocytes and natural killer cells. The induction of this immune response might be important in increasing tumor response and improving survival.

Research objectives

The aim of this study was to investigate whether HIPEC for peritoneal metastases induces an immune response, which was determined by analyzing the immune population before and 30 d after HIPEC.

Research methods

Peripheral blood samples were collected prior to (day 0) and following (day 30) CRS-HIPEC procedures, and immunophenotypic analysis was performed within 24 h. The levels of immunological populations were quantified by fluorescence-activated cell sorting, an antibody-based cell sorting method for heterogeneous mixtures based upon the specific light scattering and fluorescent characteristics of each antibody-labelled cell-type as reported in the literature. Immunological populations were also analyzed in stained samples, after exclusion of debris and doublets, as previously described.

Research results

The evaluation of system lymphocyte populations revealed an increase in systemic CD3+ total, CD3+/CD4+ T Helper, CD3+/CD8+ cytotoxic T, CD3-/CD56+ natural killer, CD19+ B lymphocyte levels and CD4+/CD8+ T lymphocyte CD3+/CD8+ Cytotoxic T lymphocyte ratios. Statistical significance was observed for CD3+/CD4+ T Helper and CD3+/CD8+ Cytotoxic T lymphocyte populations (unilateral paired Student’s t test, P < 0.05). These increases were observed in all but one patient, who exhibited reduced systemic lymphocyte counts post-HIPEC, consistent with severe oxaliplatin toxicity.

Research conclusions

The results obtained provide new evidence that HIPEC induces immune system activation in pseudomyxoma peritonei patients, characterized by induction of a generalized adaptive immune response and decrease in immunosuppression. Another new finding was that the CRS-HIPEC-induced immunological effect was long-lived and lasted for several weeks, consistently with authentic immunomodulation, rather than a normal inflammatory response.

Research perspectives

This pilot study provides the first evidence that HIPEC activates the immune response, supporting an additional immunomodulatory function for this procedure. Further studies are required to confirm these results in a large cohort study and to evaluate treatment safety, efficacy or effectiveness.