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Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
Published on: November 28, 2019
Peritonitis-induced antitumor activity of peritoneal macrophages from uremic patients
Bohdan Turyna1, Aleksandra Jurek, Kamil Gotfryd
1Department of General Biochemistry, Faculty of Biotechnology, Jagiellonian University, Cracow, Poland. bohdan@mol.uj.edu.pl
Abstract:
The macrophages belong to the effector cells of both nonspecific and specific immune response. These cells generally express little cytotoxicity unless activated. The present work was intended to determine if peritoneal macrophages collected from patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) during episodes of peritonitis were active against human tumor cell lines without further in vitro stimulation. We also compared macrophage antitumor potential with effectiveness of drugs used in cancer therapy (taxol and suramin). Conditioned medium (CM) of macrophages collected during inflammation-free periods did not exhibit cytostatic and cytotoxic activity against both tumor (A549 and HTB44) and non-transformed (BEAS-2B and CRL2190) cells. Exposure of tumor cells to CM of macrophages harvested during peritonitis resulted in significant suppression of proliferation, impairment of viability and induction of apoptosis, in contrast to non-transformed cells, which remained unaffected. The efficacy of CM of inflammatory macrophages as an antitumor agent appeared to be comparable to cytostatic and cytotoxic potency of taxol and suramin or, in the case of HTB44 cells, even higher. The results obtained suggest that activated human macrophages might represent a useful tool for cancer immunotherapy.
Insights
Peritoneal macrophages from patients with peritonitis show significant antitumor activity against human cancer cells without further stimulation. This immune cell-derived therapy shows potential comparable or superior to chemotherapy drugs.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Macrophages are key immune effector cells, typically requiring activation to exhibit cytotoxicity.
- Continuous Ambulatory Peritoneal Dialysis (CAPD) patients experiencing peritonitis present a unique model for studying activated macrophages.
Purpose of the Study:
- To investigate the in-situ antitumor potential of peritoneal macrophages from CAPD patients during peritonitis.
- To compare the efficacy of these activated macrophages against human tumor cell lines with established chemotherapy drugs like taxol and suramin.
Main Methods:
- Collected peritoneal macrophages from CAPD patients during inflammation-free periods and peritonitis episodes.
- Assessed the cytostatic and cytotoxic activity of conditioned medium (CM) from these macrophages against human tumor (A549, HTB44) and non-transformed (BEAS-2B, CRL2190) cell lines.
- Compared the antitumor effects with those of taxol and suramin.
Main Results:
- CM from macrophages during inflammation-free periods showed no significant activity against any cell lines.
- CM from macrophages during peritonitis significantly suppressed proliferation, impaired viability, and induced apoptosis in tumor cells, but not in non-transformed cells.
- The antitumor efficacy of CM from inflammatory macrophages was comparable or superior to taxol and suramin, particularly against HTB44 cells.
Conclusions:
- Human macrophages activated during peritonitis possess potent intrinsic antitumor properties.
- These activated macrophages demonstrate significant anti-cancer effects without requiring in vitro stimulation.
- Activated human macrophages represent a promising candidate for novel cancer immunotherapy strategies.

