Role of evaluating tumor‑infiltrating lymphocytes, programmed death‑1 ligand 1 and mismatch repair proteins expression in malignant mesothelioma

  • Authors:
    • Lorena Losi
    • Federica Bertolini
    • Giorgia Guaitoli
    • Luca Fabbiani
    • Federico Banchelli
    • Andrea Ambrosini‑Spaltro
    • Laura Botticelli
    • Letizia Scurani
    • Cinzia Baldessari
    • Fausto Barbieri
    • Stefano Cascinu
    • Antonino Maiorana
  • View Affiliations

  • Published online on: September 20, 2019     https://doi.org/10.3892/ijo.2019.4883
  • Pages: 1157-1164
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Abstract

The tumor immune microenvironment (TME) and immune checkpoints have been reported to serve a role in the pathogenesis of malignant mesothelioma (MM) and treatment outcome. Additionally, mismatch Repair (MMR) deficiency appears to enhance the response to checkpoints blockade in several tumors. The aim of the present study was to analyze programmed death‑1 ligand 1 (PD‑L1) expression in MM and to characterize the TME. This could help to understand the immune response, and evaluate its prognostic and predictive values. We also investigated MMR protein expression. We retrospectively analyzed 55 mesotheliomas to determine PD‑L1, CD4+, CD8+, mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6) and PMS1 homolog 2, mismatch repair system component (PMS2) expression. We used an immunoscore (1+, 2+ and 3+) to evaluate tumor‑infiltrating lymphocytes (TILs). TILs were observed in all but two samples (53/55); the majority had an immunoscore 1+ (30/53), while 2+/3+ was reported for 23/53 samples. A predominance of CD8+ was highlighted in 8 cases (15%). PD‑L1 expression of ≥1% on tumor cells was displayed in 40 cases; in 9 of these, ≥50% expression was reported. Of note, alterations in MMR staining was not observed. In addition, survival analysis revealed that epithelioid subtype was associated with better prognosis. We observed a trend towards poorer prognosis for ≥50% PD‑L1 expression on tumor cells, lower immunoscore (1+) and CD8+ TIL predominance. The present study highlighted the importance of exploring the TME and the standardization of PD‑L1 assessment guidelines to apply in the field of immunotherapy.

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November 2019
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APA
Losi, L., Bertolini, F., Guaitoli, G., Fabbiani, L., Banchelli, F., Ambrosini‑Spaltro, A. ... Maiorana, A. (2019). Role of evaluating tumor‑infiltrating lymphocytes, programmed death‑1 ligand 1 and mismatch repair proteins expression in malignant mesothelioma. International Journal of Oncology, 55, 1157-1164. https://doi.org/10.3892/ijo.2019.4883
MLA
Losi, L., Bertolini, F., Guaitoli, G., Fabbiani, L., Banchelli, F., Ambrosini‑Spaltro, A., Botticelli, L., Scurani, L., Baldessari, C., Barbieri, F., Cascinu, S., Maiorana, A."Role of evaluating tumor‑infiltrating lymphocytes, programmed death‑1 ligand 1 and mismatch repair proteins expression in malignant mesothelioma". International Journal of Oncology 55.5 (2019): 1157-1164.
Chicago
Losi, L., Bertolini, F., Guaitoli, G., Fabbiani, L., Banchelli, F., Ambrosini‑Spaltro, A., Botticelli, L., Scurani, L., Baldessari, C., Barbieri, F., Cascinu, S., Maiorana, A."Role of evaluating tumor‑infiltrating lymphocytes, programmed death‑1 ligand 1 and mismatch repair proteins expression in malignant mesothelioma". International Journal of Oncology 55, no. 5 (2019): 1157-1164. https://doi.org/10.3892/ijo.2019.4883