1619PD - Malignant Pleural Mesothelioma immune microenvironment and checkpoint expression before and after systemic cytotoxic treatment

Date 11 September 2017
Event ESMO 2017 Congress
Session Non-metastatic NSCLC and other thoracic malignancies
Topics Mesothelioma
Cancer Immunology and Immunotherapy
Lung and other Thoracic Tumours
Presenter Giulia Zago
Citation Annals of Oncology (2017) 28 (suppl_5): v568-v572. 10.1093/annonc/mdx389
Authors G. Zago1, F. Lunardi2, F. Calabrese2, S.E. Vuljan2, L. Urso3, S. Frega1, A. Pavan1, V. Polo4, L. Bonanno1, I. Attili1, F. Rea2, P.F. Conte1, G. Pasello1
  • 1Medical And Experimental Oncology Department, Medical Oncology 2, Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 2Cardiologic, Thoracic And Vascular Sciences Department, University of Padova, Padova/IT
  • 3Surgical, Oncological And Gastroenterological Sciences Department, University of Padova, Padova/IT
  • 4Surgical, Oncological And Gastroenterological Sciences Department, University of Padova, 35128 - Padova/IT

Abstract

Background

Tumor immune microenvironment (TME) plays a role in Malignant Pleural Mesothelioma (MPM) pathogenesis and patients outcome. PD1/PDL1 checkpoint inhibitors are currently under investigation as innovative promising treatment of MPM, even though no definitive predictive markers have been defined so far. PDL1 expression and TME are dynamic in tumor samples. The object of this preliminary analysis is a subset of MPM paired samples analyzed before and after induction chemotherapy (ct) in order to assess TME and PDL1 heterogeneity and dynamism over time.

Methods

Inflammatory cells in the intratumoral (IT) e peritumoral (PT) stroma were characterized by immunohistochemistry (IHC) using monoclonal anti-CD20 (B lymphocytes), CD3, CD4 and CD8 (T lymphocytes) and CD68 (macrophages) antibodies, and quantified as percentage in neoplastic area. PDL1 expression in tumor cells (TC) and immune cells (IC) was evaluated by IHC using Ventana SP263 antibody (Roche) and quantified as percentage of expressing cells. Difference between naïve and treated samples was assessed through Mann-Whithey test.

Results

15 paired MPM specimens (14 epithelioid and 1 biphasic) obtained for diagnostic purpose before platinum-pemetrexed ct and at the time of resection were analyzed. After ct MPM samples showed PT and IT increase of CD68+ macrophages and CD3+ T lymphocytes, even though only peritumoral CD3+ lymphocytes significantly increased (p=0.008). CD4+ and CD8+ lymphocytes were lacking in naive samples, while CD8+ significantly increased after ct (median value PT pre vs. post-ct: 5% vs. 30%, p=0.02; median valule IT pre vs. post-ct: 5% vs. 15%, p= 0.007). CD8+/CD68+ ratio increased after ct, even though without statistical significance. No IT B lymphocytes were observed, a small increase at PT level was shown after ct. Ct induced PDL1 expression in tumor cells and even more in lymphomonocitic infiltrate (median value pre vs. post-ct 0% vs. 50%, p=0.003).

Conclusions

Ct significantly increases cytotoxic T lymphocytes at PT and IT level in MPM samples and PDL1 expression in IC. These data confirm the strong rationale for the combination of checkpoint inhibitors and ct as promising treatment of MPM.

Clinical trial identification

not applicable

Legal entity responsible for the study

Istituto Oncologico Veneto IRCCS

Funding

None

Disclosure

All authors have declared no conflicts of interest.