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Prognostic influence of tumor microenvironment after hypofractionated radiation and surgery for mesothelioma
- Source :
- The Journal of Thoracic and Cardiovascular Surgery. 159:2082-2091.e1
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- 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).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.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+ TILs2%; 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.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.
- Subjects :
- Adult
Male
Mesothelioma
Pulmonary and Respiratory Medicine
Extrapleural Pneumonectomy
medicine.medical_specialty
Pleural Neoplasms
medicine.medical_treatment
chemical and pharmacologic phenomena
CD8-Positive T-Lymphocytes
030204 cardiovascular system & hematology
B7-H1 Antigen
03 medical and health sciences
0302 clinical medicine
PD-L1
Tumor Microenvironment
medicine
Humans
Aged
Aged, 80 and over
Tumor microenvironment
biology
Tumor-infiltrating lymphocytes
business.industry
Induction chemotherapy
Middle Aged
Prognosis
medicine.disease
Surgery
Radiation therapy
030228 respiratory system
Neoplastic Stem Cells
biology.protein
Pleura
Female
Radiation Dose Hypofractionation
Cardiology and Cardiovascular Medicine
business
CD8
Subjects
Details
- ISSN :
- 00225223
- Volume :
- 159
- Database :
- OpenAIRE
- Journal :
- The Journal of Thoracic and Cardiovascular Surgery
- Accession number :
- edsair.doi.dedup.....587dec69812ae4f5a7560813ee751dfa