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Tumour infiltrating lymphocytes and PD-L1 expression as potential predictors of outcome in patients with malignant pleural mesothelioma

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Abstract

Malignant pleural mesothelioma (MPM) is a rare and aggressive form of tumour. Some mesotheliomas have been proven to be highly immunogenic. Here, we investigated the correlation between tumour infiltrating lymphocytes (TILs) or programmed cell death ligand 1 (PD-L1) expression with overall survival (OS) in patients with MPM. 62 Paraffin-embedded formalin fixed (PEFF) samples were analysed for TILs and PD-L1 expression. Patients were divided in 4 groups according to a cut-off of the percentage of TILs found per sample as measured by immunohistichemistry: “0” or absent (between 0 and 5%), “1” or low (between 6 and 25%), “2” or moderate (between 26 and 50%) and “3” or high (between 51 and 75%). OS was then correlated with different TILs’ expression patterns. Moreover, PD-L1 expression was assessed within the tumour as well as in the adjacent stroma on the same samples. Higher expression of peritumoral TILs (Group 2 + 3) versus Group 0 and 1 correlated with improved OS (p-value = 0.02). On the contrary PD-L1 expression seemed to be inversely correlated with clinical outcomes, even in the absence of statistical significance (HR 1.76; p = 0.083 95% IC 0.92–3.36 in areas within the tumour; HR 1.60; p = 0.176 95%; IC 0.80–3.19 in areas within the stroma). No relationship between TILs and PD-L1 expression was identified. Our research supports the use of TILs and PD-L1 expression as potential outcome predictors in patients with MPM. The use of TILs and PD-L1 as biomarkers for checkpoint inhibitors’ efficacy warrants future investigation.

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Acknowledgements

Supported by Fondazione “Aldo Duca” and Progetto FRA 2016–2017, Dipartimento Universitario Clinico di Scienze Mediche, Chirurgiche e della Salute, Università degli Studi di Trieste.

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Authors and Affiliations

  1. Department of Medicine, Surgery & Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy

    N. Sobhani, T. Pivetta, D. Bonazza, F. Zanconati, F. Giudici, C. Bottin, S. P. Corona, C. Rizzardi, M. Cortale & M. Confalonieri

  2. Department of Medicine, Surgery & Health Sciences, University of Trieste, Piazza Ospitale 1, 34129, Trieste, Italy

    N. Sobhani, G. Roviello, A. Ianza, A. Guglielmi & D. Generali

  3. Division of Medical Oncology, Department of Onco-Hematology, IRCCS-CROB, Referral Cancer Center of Basilicata, via Padre Pio 1, 85028, Rionero in Vulture, PZ, Italy

    G. Roviello

  4. Pathology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    M. Milione

  5. Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy

    D. Generali

  6. Breast Cancer Unit and Translational Research Unit, ASST Cremona, Cremona, Italy

    D. Generali

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  1. N. Sobhani
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Sobhani, N., Roviello, G., Pivetta, T. et al. Tumour infiltrating lymphocytes and PD-L1 expression as potential predictors of outcome in patients with malignant pleural mesothelioma. Mol Biol Rep 46, 2713–2720 (2019). https://doi.org/10.1007/s11033-019-04715-9

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