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.
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.
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).
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
Legal entity responsible for the study
Istituto Oncologico Veneto IRCCS
All authors have declared no conflicts of interest.