8515 Background: Studies using immune checkpoint inhibitors in mesothelioma (MM) have shown promise. Differences in response to PD-L1 and PD-1 inhibitors (10% vs 25%) have been reported. Also, expression of PD-L1 alone appears to be a limited predictor. As the roles of the multiple check point receptors and their ligands become defined, an understanding of their expression and interplay in the mm tumour microenvironment, which could affect suitability for checkpoint inhibition therapy, has become necessary. Methods: Tissue microarrays were constructed and stained with PD-L2, LAG3 and TIM3 antibodies. Tumour infiltrating lymphocytes (TILs) were assessed in the stroma and expressed as a % of stromal area within invasive tumour. These data were combined with PD-L1 expression, CD4+ and CD8+ infiltration in the same cohort reported previously. To quantify the immunosuppressive milieu, we combined our assessment of PD-L1, PD-L2 and TIM3 expression to derive an “Immune checkpoint score (ICS)” and explored its correlation with the tumour microenvironment and clinicopathological covariates. We are also exploring its predictive value in an independent cohort of mm patients who have received anti-PD-1 treatment. Results: Amongst 329 patients evaluated, PD-L1 was positive (+) in 41.7% and PD-L2+ in 24.5%. TIM3+ lymphocytes were found in 99.4% but LAG3+ lymphocytes in only 0.2%. 28/173 (16%) of PD-L1- patients were PD-L2+ and 31/136 (22%) PD-L1 and PD-L2 negative patients had high infiltration with TIM3+ lymphocytes. High ICS was associated with non-epithelioid histology, increased TILs and poorer survival. On multivariate analysis, high TILs, non-epithelioid histology and poor physiological status remained significantly associated with poorer survival. Data on the predictive role of ICS score will also be reported. Conclusions: While co-expression of PD-L1, PD-L2 and TIM3 can occur, their expression is mutually exclusive in a large proportion of patients. The expression of PD-L2 may explain differences in responses seen between PD-1 compared to PD-L1 inhibitors. A comprehensive assessment of these multiple immunosuppressive pathways may be necessary to truly gauge the immunosuppressive environment and tailor immunotherapy for individual cases.
PSEUDO PAPILLARY TUMOUR OF PANCREAS
