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Autoimmune response in lung cancer patients with neurological paraneoplastic syndromes
Affiliations- Department of Neurology, Division of Neurochemistry and Neuropathology, Poznan Univerisity of Medical Sciences, 49, Przybyszewskiego st., 60-355 Poznan, Poland
- Department of Pulmonology, Allergology and Respiratory Oncology, Poznan University of Medical Sciences, Poland, Poznan, Poland
- Department of Gynecologic Oncology, Chair of Gynecology, Obstetrics and Gynecologic Oncology, Poznan University of Medical Sciences, Poznan, Poland
- Department of Neurology, Poznan, Poland
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Abstract
Aim of the study. The aim of this study was to evaluate granzyme B, perforin and FasL expression in peripheral blood mononuclear cells (PBMCs) in lung cancer patients and in paraneoplastic neurological syndromes (PNS).
Clinical rationale for the study. Cellular immune response is activated as part of anti-tumour reaction of the malignancy-bearing host. Paraneoplastic neurological syndromes (PNS) are defined as indirect effects of cancer on the nervous system and are considered immune-mediated. Such stimulation of the immune system may limit the aggressiveness of cancer and the development of metastasis, and thereby improve survival. Granzyme B and perforin pathway, and Fas ligand (FasL) – Fas receptor interaction play an important role in cytotoxic response.
Materials and Methods. Fifty-two patients were included in the study: 28 subjects with PNS and 24 subjects with lung cancer. PNS cases were diagnosed according to the Graus criteria. The presence of onconeural antibodies (anti-Hu/anti-Ri/anti-Yo/anti-Ma/Ta/anti-CV2/anti-amphiphysin/anti-myelin/anti-neuroendothelium/anti-MAG/anti-GAD) was detected with indirect immunofluorescence and confirmed with Line Blotting. The expression of granzyme B, perforin and FasL was detected in PBMCs with ELISA.
Results. PPBMC-FasL expression was increased in lung cancer compared to other patient groups. The granzyme to FasL ratio was significantly higher in lung cancer patients with peripheral than with central PNS involvement. In a multiple regression model, sex was an independent factor influencing PBMC expression of granzyme and perforin.
Conclusions. FasL expression in PBMCs is up-regulated in lung cancer patients. The interplay between granzyme B and FasL may be involved in the development of PNS at the level of the peripheral and the central nervous systems in different manners. Gender is associated with PBMC expression of granzyme B and perforin in lung cancer patients.
Clinical Implications. The novel findings that we report broaden the current knowledge on PNS pathomechanism, with aspects that have not been previously explored. Our findings provide a rationale for further exploration of the granzyme B/FasL pathway with regards to its potential diagnostic value. However, our study is preliminary and needs further research, especially in the context of the prognostic value of the proposed markers.
Abstract
Aim of the study. The aim of this study was to evaluate granzyme B, perforin and FasL expression in peripheral blood mononuclear cells (PBMCs) in lung cancer patients and in paraneoplastic neurological syndromes (PNS).
Clinical rationale for the study. Cellular immune response is activated as part of anti-tumour reaction of the malignancy-bearing host. Paraneoplastic neurological syndromes (PNS) are defined as indirect effects of cancer on the nervous system and are considered immune-mediated. Such stimulation of the immune system may limit the aggressiveness of cancer and the development of metastasis, and thereby improve survival. Granzyme B and perforin pathway, and Fas ligand (FasL) – Fas receptor interaction play an important role in cytotoxic response.
Materials and Methods. Fifty-two patients were included in the study: 28 subjects with PNS and 24 subjects with lung cancer. PNS cases were diagnosed according to the Graus criteria. The presence of onconeural antibodies (anti-Hu/anti-Ri/anti-Yo/anti-Ma/Ta/anti-CV2/anti-amphiphysin/anti-myelin/anti-neuroendothelium/anti-MAG/anti-GAD) was detected with indirect immunofluorescence and confirmed with Line Blotting. The expression of granzyme B, perforin and FasL was detected in PBMCs with ELISA.
Results. PPBMC-FasL expression was increased in lung cancer compared to other patient groups. The granzyme to FasL ratio was significantly higher in lung cancer patients with peripheral than with central PNS involvement. In a multiple regression model, sex was an independent factor influencing PBMC expression of granzyme and perforin.
Conclusions. FasL expression in PBMCs is up-regulated in lung cancer patients. The interplay between granzyme B and FasL may be involved in the development of PNS at the level of the peripheral and the central nervous systems in different manners. Gender is associated with PBMC expression of granzyme B and perforin in lung cancer patients.
Clinical Implications. The novel findings that we report broaden the current knowledge on PNS pathomechanism, with aspects that have not been previously explored. Our findings provide a rationale for further exploration of the granzyme B/FasL pathway with regards to its potential diagnostic value. However, our study is preliminary and needs further research, especially in the context of the prognostic value of the proposed markers.
Keywords
lung cancer, paraneoplastic neurological syndromes, cytotoxicity, onconeural antibodies, Fas ligand, granzyme B, perforin
About this articleTitle
Autoimmune response in lung cancer patients with neurological paraneoplastic syndromes
Journal
Neurologia i Neurochirurgia Polska
Issue
Article type
Research Paper
Pages
217-226
Published online
2019-06-12
Page views
1878
Article views/downloads
413
DOI
Pubmed
Bibliographic record
Neurol Neurochir Pol 2019;53(3):217-226.
Keywords
lung cancer
paraneoplastic neurological syndromes
cytotoxicity
onconeural antibodies
Fas ligand
granzyme B
perforin
Authors
Sławomir Michalak
Tomasz Piorunek
Mikołaj Zaborowski
Joanna Rybacka-Mossakowska
Patrycja Stefens-Stawna
Alicja Kalinowska-Łyszczarz
Wojciech Kozubski
Halina Batura-Gabryel
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