Role of evaluating tumor infiltrating lymphocytes, programmed death-ligand 1 and MisMatchRepair proteins expression in malignant mesothelioma

Date 20 October 2018
Event ESMO 2018 Congress
Session Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Topics Tumour Immunology
Mesothelioma
Presenter Lorena Losi
Citation Annals of Oncology (2018) 29 (suppl_8): viii641-viii644. 10.1093/annonc/mdy301
Authors L. Losi1, F. Bertolini2, L. Scurani1, G. Guaitoli2, C. Baldessari2, A. Ambrosini Spaltro3, L. Botticelli3, A. Maiorana3, F. Barbieri2, S. Cascinu2
  • 1Department Of Life Sciences, Unit Of Pathology, University of Modena and Reggio Emilia, 41124 - Modena/IT
  • 2Department Of Oncology And Haematology, Azienda Ospedaliero - Universitaria Policlinico di Modena, 41124 - Modena/IT
  • 3Department Of Diagnostic Medicine, Clinic And Public Health, Unit Of Pathology, University of Modena and Reggio Emilia, Modena/IT

Abstract

Background

Malignant mesothelioma (MM) is an aggressive and fatal tumor, mainly related to prolonged exposure to asbestos. MM can induce infiltration of immune cells and immunity-mediated death. Tumor microenvironment plays a major role in neoplastic progression, favoring tumor cell evasion from adaptive immunity and T-cell checkpoint pathways. Expression of programmed death-ligand 1 (PD-L1) on tumor cells and tumor-infiltrating lymphocytes (TILs) has been described in literature. Cancer cells expressing PD-L1 increase apoptosis of antigen-specific human T-cell clones and inhibit CD4+ and CD8+ T-cell activation, thus decreasing the immune action on the tumor cells. Some mismatch repair–deficient tumors make them sensitive to immune checkpoint blockade, because of the increased number of neoantigens encoded by cancers, which enhances anti-tumor response.

Methods

The aim of this study is to analyze the expression of PD-L1 on both tumor cells and TILs and to characterize TILs. Furthermore, MisMatchRepair (MMR) protein expression was evaluated. Immunohistochemistry was applied using the automated system BenchMark XT (VENTANA) for PD-L1 (DAKO, clone 22C3), CD4, CD8 and MLH1, MSH2, MSH6, PMS2.

Results

55 malignant mesotheliomas, 10 from women and 45 from men, were studied. The range of age was 43-88 years old. Tumors consisted of 44 epithelioid, 3 sarcomatoid, 7 biphasic and 1 desmoplastic. 51 were localized to pleura and 4 to peritoneum. 18 tumors were in stage I, 13 in stage II, 15 in stage III and 5 in stage IV. For 4 cases the stage was not evaluable. Our results showed expression of PD-L1 ≥50% in tumor cells in 9 cases (5 epithelioid, 2 sarcomatoid, 1 biphasic and 1 desmoplastic). In two of these the positivity was observed both in tumor cells and in TILs. 15 tumors were negative and 31 showed a positive staining ≥1. A presence of TILs was observed in 53 cases. A prevalence of CD4+ expression was highlighted in 45 cases. 6 of them showed elevated expression of PD-L1 (≥50%). Alteration in MMR staining was not found.

Conclusions

Our data underline the role of tumor immune microenvironment and its characterization in MM and open the possibility to use combined therapies according to different PD-L1 expression.

Clinical trial identification

Legal entity responsible for the study

Modena University Hospital.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.