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
Abstract
BACKGROUND

Hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastases (PM) is considered to be feasible, safe and to improve survival.

AIM

To investigate whether an immune response is activated following HIPEC for PM.

METHODS

Six patients were enrolled in this study. Peripheral blood samples were obtained from each patient prior to (day 0) and post-procedure (day 30), and used to evaluate the number of CD3+ total, CD3+/CD4+ T-Helper, CD3+/CD8+ cytotoxic T, CD3+/CD56+ natural killer and CD19+ B lymphocyte numbers, and CD4+: CD8+ T lymphocyte ratios.

RESULTS

The total numbers of CD3+, CD3+/CD4+ T-Helper, CD3+/CD8+ cytotoxic T, CD3+/CD56+ natural killer and CD19+ B lymphocytes, and CD4+: CD8+ lymphocyte ratios were increased in all but one patient 30 d following the cytoreductive surgery-HIPEC procedure, and these increases were significant (P ≤ 0.05) for CD3+/CD4+ T Helper and CD3+/CD8+ cytotoxic T lymphocyte numbers.

CONCLUSION

This report provides the first evidence that HIPEC exhibits immunomodulating activity in PM patients, resulting in generalized activation of the adaptive immune response. Moreover, the majority of lymphocyte populations increased following HIPEC and continued to be elevated several weeks following the procedure, consistent with a potential authentic immunomodulating effect rather than a normal inflammatory response, to be fully characterised in future studies.

Keywords: Immune response, Hyperthermic intraperitoneal chemotherapy, Peritoneal metastases, Regulatory T lymphocytes, Pseudomyxoma peritonei, Colorectal cancer

Core tip: Reports indicate that thermal tumor ablation has potential immunomodulatory activity, illustrated by the intense inflammatory cell response that is associated with this procedure, and characterized by thermally ablated tissue transitional zone infiltration by immunological and inflammatory cell populations, including: Dendritic cells, neutrophils, macrophages, B and T lymphocytes and natural killer cells. In the present study, we evaluated and confirm that hyperthermic intraperitoneal chemotherapy for peritoneal metastases also exhibits immunomodulatory activity, inducing the general activation of an adaptive immune response.