Treatment-specific Association of H&E-based Stromal Tumor-infiltrating Lymphocytes With Survival in Pleural Mesothelioma Treated With Ipilimumab/Nivolumab or Chemotherapy

Background/Aim: Pleural mesothelioma lacks robust biomarkers to guide personalized treatment selection. Although stromal tumor-infiltrating lymphocytes (sTILs) on hematoxylin and eosin (H&E)-stained sections represent a cost-effective biomarker in various cancers, their clinical significance in pleural mesothelioma remains unclear. This study evaluated the prognostic impact of sTILs in pleural mesothelioma patients treated with platinum-pemetrexed chemotherapy or dual immune checkpoint inhibition (ICI) using ipilimumab plus nivolumab (Ipi/Nivo). Patients and Methods: We retrospectively analyzed 179 patients with unresectable pleural mesothelioma who received either platinum-pemetrexed chemotherapy (n=127) or Ipi/Nivo (n=52). sTILs were assessed according to the International TILs Working Group guidelines and categorized as high (>10%) or low (≤10%). Overall survival (OS) and associations between sTIL status and clinicopathological characteristics were evaluated. Results: High and low sTIL status was observed in 82 (45.8%) and 97 (54.2%) patients, respectively. Within each treatment cohort, baseline clinicopathological characteristics were generally well-balanced according to sTIL status. In the entire cohort, sTIL status was not significantly associated with OS (p=0.559). Subgroup analyses according to treatment modality showed no significant association between sTIL status and OS in the platinum-pemetrexed cohort (p=0.664). In contrast, in the Ipi/Nivo cohort, OS was significantly longer in the low sTIL group than in the high sTIL group (p=0.027). Conclusion: sTILs may have treatment-specific prognostic significance in pleural mesothelioma. Notably, low sTIL status was associated with longer survival among patients treated with dual ICI but not chemotherapy. Standardized H&E-based sTIL assessment may provide a simple and accessible approach for refining treatment selection in pleural mesothelioma.