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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/26302

Title: Abundant expression of TIM-3, LAG-3, PD-1 and PD-L1 as immunotherapy checkpoint targets in effusions of mesothelioma patients
Authors: Marcq, Elly
De Waele, Jorrit
Van Audenaerde, Jonas
Lion, Eva
Santermans, Eva
Hens, Niel
Pauwels, Patrick
van Meerbeeck, Jan P.
Smits, Evelien L. J.
Issue Date: 2017
Publisher: IMPACT JOURNALS LLC
Citation: ONCOTARGET, 8(52), p. 89722-89735
Abstract: Malignant pleural mesothelioma (MPM) is an aggressive cancer with an increasing incidence, poor prognosis and limited effective treatment options. Hence, new treatment strategies are warranted which include immune checkpoint blockade approaches with encouraging preliminary data. Research on the immunological aspects of the easily accessible mesothelioma microenvironment could identify prognostic and/or predictive biomarkers and provide useful insights for developing effective immunotherapy. In this context, we investigated the immune cell composition of effusions (pleural and ascites fluids) from 11 different chemotherapy-treated MPM patients. We used multicolor flow cytometry to describe different subsets of immune cells and their expression of immune checkpoint molecules TIM-3, LAG-3, PD-1 and PD-L1. We demonstrate a patient-dependent inter-and intraspecific variation comparing pleural and ascites fluids in immune cell composition and immune checkpoint expression. We found CD4(+) and CD8(+) T cells, B cells, macrophages, natural killer cells, dendritic cells and tumor cells in the fluids. To the best of our knowledge, we are the first to report TIM-3 and LAG-3 expression and we confirm PD-1 and PD-L1 expression on different MPM effusion-resident immune cells. Moreover, we identified two MPM effusion-related factors with clinical value: CD4(+) T cells were significantly correlated with better response to chemotherapy, while the percentage of PD-L1(+) podoplanin (PDPN)(+) tumor cells is a significant prognostic factor for worse outcome. Our data provide a basis for more elaborate research on MPM effusion material in the context of treatment follow-up and prognostic biomarkers and the development of immune checkpoint-targeted immunotherapy.
Notes: [Marcq, Elly; De Waele, Jorrit; Van Audenaerde, Jonas; Pauwels, Patrick; van Meerbeeck, Jan P.; Smits, Evelien L. J.] Univ Antwerp, Ctr Oncol Res, Antwerp, Belgium. [Lion, Eva; Smits, Evelien L. J.] Univ Antwerp, Lab Expt Hematol, Antwerp, Belgium. [Santermans, Eva; Hens, Niel] Hasselt Univ, Interuniv Inst Biostat & Stat Bioinformat, Diepenbeek, Belgium. [Hens, Niel] Univ Antwerp, Ctr Hlth Econ Res & Modelling Infect Dis, Antwerp, Belgium. [Pauwels, Patrick] Antwerp Univ Hosp, Dept Pathol, Antwerp, Belgium. [van Meerbeeck, Jan P.] Antwerp Univ Hosp, Thorac Oncol MOCA, Antwerp, Belgium.
URI: http://hdl.handle.net/1942/26302
DOI: 10.18632/oncotarget.21113
ISI #: 000414097100027
ISSN: 1949-2553
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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