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RESEARCH PRODUCT
Analysis of the immune microenvironment in resected non-small cell lung cancer: the prognostic value of different T lymphocyte markers
Roy M. BremnesSilvia CalabuigJerónimo FortezaRafael SireraRicardo GuijarroIrene BorredaLuis Paz-aresAna BlascoSonia Molina-pineloEnrique PastorMiguel MartorellMarta UsóEloisa Jantus-lewintreCarlos Campssubject
0301 basic medicineMalePathologyLung NeoplasmsT-LymphocytesBIOLOGIA CELULARKaplan-Meier EstimateNSCLC0302 clinical medicineT-Lymphocyte SubsetsCarcinoma Non-Small-Cell LungTumor MicroenvironmentCytotoxic T cellAged 80 and overFOXP3Forkhead Transcription FactorsMiddle AgedPrognosismedicine.anatomical_structureOncology030220 oncology & carcinogenesisCD4 AntigensFemaleAdultmedicine.medical_specialtyStromal cellRegulatory T cellCD8 Antigensimmune-biomarkerPrognostic03 medical and health sciencesImmune systemmedicineBiomarkers TumorResearch Paper: Autophagy and Cell DeathHumansImmune biomarkerTumor stromaTumor compartmentAgedTumor microenvironmentbusiness.industryVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762tumor stromaCancermedicine.disease030104 developmental biologyImmune-biomarkerCancer researchimmunebusinessprognosticCD8description
[EN] The prognosis of non-small cell lung cancer (NSCLC) remains poor and heterogeneous and new biomarkers are needed. As the immune system plays a pivotal role in cancer, the study of immune-related markers may provide valuable prognostic information of NSCLC. In 122 formalin-fixed, paraffin-embedded tumor tissue samples from early-stage NSCLC, tumor and tumor-near stromal areas were microdissected and gene expression levels of conventional and regulatory T cell markers were assessed by quantitative polymerase chain reaction. Also, the presence of infiltrating CD4+, CD8+, and FOXP3+ cells in tumor samples was assessed by immunohistochemistry. The relative proportion of conventional and regulatory T cells present in the tumor environment was assessed and found to be key to understand the importance that the immune system analysis has in the prognostics of NSCLC patients. The presence of CD8+ cells in the tumor compartment was associated with better outcome, whereas the presence of FOXP3+ cells was associated with worse overall survival. The negative prognostic value of combined biomarkers, indicating high levels of FOXP3 in the stroma and low levels of CD4 or CD8 in tumors, was observed at mRNA level and was validated by immunohistochemistry. In conclusion, the proportion of T helper and cytotoxic cells vs. regulatory T cells in different locations of the tumor microenvironment have opposite prognostic impacts in resected NSCLC.
year | journal | country | edition | language |
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2016-08-16 |