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C. Riganti
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P2.09 - Mesothelioma (ID 710)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.09-003 - Dissecting the Immune Environment in Malignant Pleural Mesothelioma: Results from a Prospective Assessment (ID 8256)
09:30 - 09:30 | Author(s): C. Riganti
- Abstract
Background:
Malignant pleural mesothelioma (MPM) cells grow in the context of immune cells, either infiltrating the tumor or present in the associated pleural effusion. Specific immune cell subsets and immune-checkpoints on T-lymphocytes infiltrating the tumor have been proposed as possible prognostic factors (Uiije, DOI:10.1080/2162402X.2015.1009285; Awad, DOI:10.1158/2326-6066.CIR-16-0171) and therapeutic targets (Marcq, DOI:10.1080/2162402X.2016.1261241; Khanna, DOI: 10.1016/j.jtho.2016.07.033). The immune cells infiltrating MPM are however dynamically exchanged with those present in the pleural fluid (Lievense, DOI: 10.1016/j.lungcan.2016.04.015). The heterogeneity of tumor bulk, ranging from terminally differentiated cells to tumor-initiating cells (TIC), makes the interactions between tumor and immune cells even more jeopardized. Our study is the first that analyzes at the same time the immune-phenotype of MPM cells, immune cells infiltrating the tumor and present in the matched pleural fluid, to obtain a comprehensive signature of MPM immune-environment and precise indications for personalized immunotherapy-based interventions.
Method:
From June 2015 to June 2017, we collected 120 pleural fluids and biopsies from patients that undergone diagnostic thoracoscopy: 34 samples were diagnosed as MPM (25 epithelioid, 5 sarcomatoid, 4 biphasic MPM), 56 samples were reactive non neoplastic pleuritis, 30 samples were pleural localization of lung adenocarcinoma or other tumors. Cells of pleural fluids were analyzed by cell sorting and flow cytometry. Biopsies were cut and digested, and cell populations were analyzed as well. We isolated, expanded and analyzed the TIC-component from 5 epithelioid and 5 sarcomatoid MPM.
Result:
MPM significantly differed from non neoplastic pleuritis for the increased number of CD3[+]CD8[+]T-lymphocytes in pleural essudate coupled with the reduction of this population within the tumor (p<0.001). M2/M1-macrophages ratio was also higher (p<0.02). The increased number of T-regulatory cells and granulocytic/monocytic myeloid-derived suppressor cells in both pleural fluid and tumor significantly (p<0.005) differentiated MPM from non neoplastic pleuritis and other malignancies. Either CD3[+]CD8[+]or CD3[+]CD4[+]T-lymphocytes present in pleural fluid and infiltrating the tumor had higher expression of PD-1, LAG-3, TIM-3 immune-checkpoints (p< 0.02), coupled with increased expression of PD-1L, LAG-3, TIM-3 and GAL-9 on matched MPM (p<0.05) compared to non neoplastic pleuritis. Interestingly, immune-checkpoints were down-regulated in TIC, suggesting that immune-checkpoint inhibitors may be poorly effective against this MPM component.
Conclusion:
Our study identified an immune-signature that discriminates MPM from pleuritis secondary to other tumors or non malignant diseases. Such immune-signature will help to refine prognostic factors and define a precision immunotherapy for MPM.
