Marc de Perrot1, Licun Wu2, Michael Cabanero3, J Yannis Perentes4, Trevor D McKee5, Laura Donahoe4, Penelope Bradbury6, Mikihiro Kohno2, Mei-Lin Chan2, Junichi Murakami2, Shaf Keshavjee7, Ming-Sound Tsao3, B C John Cho8. 1. Division of Thoracic Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada; Latner Thoracic Surgery Laboratories, University Health Network, University of Toronto, Toronto, Ontario, Canada; Department of Immunology, University of Toronto, Toronto, Ontario, Canada. Electronic address: marc.deperrot@uhn.ca. 2. Latner Thoracic Surgery Laboratories, University Health Network, University of Toronto, Toronto, Ontario, Canada. 3. Department of Pathology, University Health Network, University of Toronto, Toronto, Ontario, Canada. 4. Division of Thoracic Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada. 5. STTARR Program, University Health Network, University of Toronto, Toronto, Ontario, Canada. 6. Division of Medical Oncology, University Health Network, University of Toronto, Toronto, Ontario, Canada. 7. Division of Thoracic Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada; Latner Thoracic Surgery Laboratories, University Health Network, University of Toronto, Toronto, Ontario, Canada. 8. Department of Radiation Oncology, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Abstract
OBJECTIVE: Cytotoxic CD8+ tumor infiltrating lymphocytes (TILs) can contribute to the benefit of hypofractionated radiation, but programmed cell death pathways (programmed cell death 1 and programmed cell death ligand 1 [PD-1/PD-L1]) may provide a mechanism of tumor immune escape. We therefore reviewed the influence of PD-1/PD-L1 and CD8+ TILs on survival after accelerated hypofractionated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma (MPM). METHODS: Sixty-nine consecutive patients undergoing the protocol of Surgery for Mesothelioma after Radiation Therapy (SMART) between November 2008 and February 2016 were analyzed for the presence of PD-L1 on tumor cells, PD-1 on inflammatory cells, and CD8+ TILs. Comparison was made with a cohort of patients undergoing extrapleural pneumonectomy after induction chemotherapy (n = 14) and no induction (n = 2) between March 2005 and October 2008. PD-L1 expression on tumor cells ≥1% was considered positive. CD8+ TILs and PD-1 expression were scored as a percentage of positive cells. RESULTS: PD-L1 was negative in 75% of MPM after completion of SMART. CD8+ TILs ranged between 0.24% and 8.47% (median 2%). CD8+ TILs ≥2% was associated with significantly better survival in epithelioid MPM (median survival 3.7 years vs 2.3 years in CD8+ TILs <2%; P = .02). PD-L1 positivity was associated with worse survival in biphasic MPM (median survival, 0.4 years vs 1.5 years in biphasic PD-L1 negative tumors; P = .07) after SMART. Multivariate analysis demonstrated that epithelioid MPM, nodal disease, and CD8+ TILs were independent predictors of survival after SMART. CONCLUSIONS: The influence of tumor microenvironment on survival differs between epithelioid and nonepithelioid MPM. CD8+ TILs is an independent factor associated with better survival in epithelioid MPM treated with SMART.
OBJECTIVE:CytotoxicCD8+ tumor infiltrating lymphocytes (TILs) can contribute to the benefit of hypofractionated radiation, but programmed cell death pathways (programmed cell death 1 and programmed cell death ligand 1 [PD-1/PD-L1]) may provide a mechanism of tumor immune escape. We therefore reviewed the influence of PD-1/PD-L1 and CD8+ TILs on survival after accelerated hypofractionated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma (MPM). METHODS: Sixty-nine consecutive patients undergoing the protocol of Surgery for Mesothelioma after Radiation Therapy (SMART) between November 2008 and February 2016 were analyzed for the presence of PD-L1 on tumor cells, PD-1 on inflammatory cells, and CD8+ TILs. Comparison was made with a cohort of patients undergoing extrapleural pneumonectomy after induction chemotherapy (n = 14) and no induction (n = 2) between March 2005 and October 2008. PD-L1 expression on tumor cells ≥1% was considered positive. CD8+ TILs and PD-1 expression were scored as a percentage of positive cells. RESULTS:PD-L1 was negative in 75% of MPM after completion of SMART. CD8+ TILs ranged between 0.24% and 8.47% (median 2%). CD8+ TILs ≥2% was associated with significantly better survival in epithelioid MPM (median survival 3.7 years vs 2.3 years in CD8+ TILs <2%; P = .02). PD-L1 positivity was associated with worse survival in biphasic MPM (median survival, 0.4 years vs 1.5 years in biphasic PD-L1 negative tumors; P = .07) after SMART. Multivariate analysis demonstrated that epithelioid MPM, nodal disease, and CD8+ TILs were independent predictors of survival after SMART. CONCLUSIONS: The influence of tumor microenvironment on survival differs between epithelioid and nonepithelioid MPM. CD8+ TILs is an independent factor associated with better survival in epithelioid MPM treated with SMART.
Authors: Aaron S Mansfield; Rebecca J Brown; Cormac Sammon; Melinda J Daumont; Mike McKenna; Jenine K Sanzari; Patrick M Forde Journal: JTO Clin Res Rep Date: 2022-03-22