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|Title: ||Prognostic and predictive aspects of the tumor immune microenvironment and immune checkpoints in malignant pleural mesothelioma|
|Authors: ||Marcq, Elly|
De Waele, Jorrit
van Audenaerde, Jonas
van Meerbeeck, Jan P.
Smits, Evelien L. J.
|Issue Date: ||2017|
|Publisher: ||TAYLOR & FRANCIS INC|
|Citation: ||ONCOIMMUNOLOGY, 6(1), p. 1-11 (Art N° e1261241)|
|Abstract: ||Malignant pleural mesothelioma (MPM) is an aggressive cancer with a poor prognosis and an increasing incidence, for which novel therapeutic strategies are urgently required. Since the immune system has been described to play a presumed role in the protection against MPM, characterization of its tumor immune microenvironment (TME) and immune checkpoints can identify new immunotherapeutic targets and their predictive and/or prognostic value. To characterize the TME and the immune checkpoint expression profile, we performed immunohistochemistry (IHC) on formalin-fixed paraffin embedded (FFPE) tissue sections from 54 MPM patients (40 at time of diagnosis; 14 treated with chemotherapy). We stained for PD-1, PD-L1, TIM-3, LAG-3, CD4, CD8, CD45RO, granzyme B, FoxP3 and CD68. Furthermore, we analyzed the relationship between the immunological parameters and survival, as well as response to chemotherapy. We found that TIM-3, PD-1 and PD-L1 were expressed on both immune and tumor cells. Strikingly, PD-1 and PD-L1 expression on tumor cells was only seen in unpretreated samples. No LAG-3 expression was observed. CD45RO expression in the stroma was an independent negative predictive factor for response on chemotherapy, while CD4 and TIM-3 expression in lymphoid aggregates were independent prognostic factors for better outcome. Our data propose TIM-3 as a promising new target in mesothelioma. Chemotherapy influences the expression of immune checkpoints and therefore further research on the best combination treatment schedule is required.|
|Notes: ||[Marcq, Elly; Siozopoulou, Vasiliki; De Waele, Jorrit; van Audenaerde, Jonas; Zwaenepoel, Karen; Pauwels, Patrick; van Meerbeeck, Jan P.; Smits, Evelien L. J.] Univ Antwerp, Ctr Oncol Res, Antwerp, Belgium. [Siozopoulou, Vasiliki; Zwaenepoel, Karen; Pauwels, Patrick] Univ Antwerp Hosp, Dept Pathol, Antwerp, Belgium. [Santermans, Eva; Hens, Niel] Hasselt Univ, Interunivers Inst Biostat & Stat Bioinformat, Diepenbeek, Belgium. [Hens, Niel] Univ Antwerp, Vaccine & Infect Dis Inst, Ctr Hlth Econ Res & Modeling Infect Dis, Antwerp, Belgium. [van Meerbeeck, Jan P.] Univ Antwerp Hosp, MOCA, Thorac Oncol, Antwerp, Belgium. [Smits, Evelien L. J.] Univ Antwerp, Vaccine & Infect Dis Inst, Lab Expt Hematol, Antwerp, Belgium.|
|ISI #: ||000397069400023|
|Type: ||Journal Contribution|
|Appears in Collections: ||Research publications|
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