6533b858fe1ef96bd12b5b72
RESEARCH PRODUCT
Residual tumor micro-foci and overwhelming regulatory T lymphocyte infiltration are the causes of bladder cancer recurrence
Simonato AlchiedeGiuseppina ConteducaFrancesca FerreraFrancesca KalliDaniela FenoglioCristina BernardiLuca MastracciGilberto FilaciPaolo TraversoMonica CurtoSamuele TarditoGiovanni CarmignaniFederica GrilloAlessia ParodiFrancesco MinagliaGiorgia Nasisubject
0301 basic medicinePathologyNeoplasm ResidualT-LymphocytesMessengerImmunoenzyme TechniqueFluorescent Antibody TechniqueCD8-Positive T-LymphocytesT-Lymphocytes RegulatoryImmunoenzyme TechniquesTh10302 clinical medicineLymphocytesReverse Transcriptase Polymerase Chain ReactionResearch Paper: ImmunologyPrognosisRegulatoryBladder cancer; Immune response; Immunity; Immunology and microbiology section; Mage; Th1; Th17; Tumor infiltrating lymphocytes; CD8-Positive T-Lymphocytes; Case-Control Studies; Fluorescent Antibody Technique; Follow-Up Studies; Humans; Immunoenzyme Techniques; Lymphocytes Tumor-Infiltrating; Melanoma-Specific Antigens; Neoplasm Grading; Neoplasm Proteins; Neoplasm Recurrence Local; Neoplasm Staging; Neoplasm Residual; Prognosis; RNA Messenger; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes Regulatory; Urinary Bladder Neoplasms; OncologyNeoplasm Proteinsmedicine.anatomical_structureLocalOncologytumor infiltrating lymphocytesResidual030220 oncology & carcinogenesisImmunology and Microbiology Sectionbladder cancerTh17Case-Control StudieMelanoma-Specific AntigenMelanoma-Specific AntigensHumanmedicine.medical_specialtyPrognosiRegulatory T cellT cellReal-Time Polymerase Chain ReactionMAGEFollow-Up StudieNeoplasm Protein03 medical and health sciencesLymphocytes Tumor-InfiltratingImmune systemAntigenmedicineHumansTumor-InfiltratingRNA MessengerImmune responseNeoplasm StagingBladder cancerTumor-infiltrating lymphocytesbusiness.industryImmunityCD8-Positive T-LymphocyteT lymphocytemedicine.diseaseNeoplasm Recurrence030104 developmental biologyUrinary Bladder NeoplasmsCase-Control StudiesNeoplasmRNANeoplasm GradingNeoplasm Recurrence Localtumor infiltrating lymphocytebusinessCD8Follow-Up Studiesdescription
Bladder cancer has an unexplained, high recurrence rate. Causes of recurrence might include the presence of sporadic tumor micro-foci in the residual urothelial tissue after surgery associated with an inverted ratio between intratumoral effector and regulatory T cell subsets. Hence, surgical specimens of both tumors and autologous, macroscopically/histologically free-of-tumor tissues were collected from 28 and 20 patients affected by bladder or renal cancer, respectively. The frequencies of effector (IFNγ+ and IL17+ T cells) and regulatory (CD4+CD25hiCD127lo and CD8+CD28-CD127loCD39+ Treg) T cell subpopulations among tumor infiltrating lymphocytes were analyzed by immunofluorescence, while the gene expression of MAGE-A1 and MAGE-A2 tumor-associated antigens was studied by RT-PCR. The results show that both the T cell infiltrate and the frequency of MAGE-A1/A2 gene expression were comparable in tumors and in autologous free-of-tumor tissues in bladder cancer, while the autologous free-of-tumor renal tissues showed reduced T cell infiltrate and frequency of MAGE gene expression as compared to the autologous tumors. Importantly, the intra-tumor T effector/Treg cell ratio was consistently <1 in bladder cancer patients (n. 7) who relapsed within two years, while it was always >1 in patients (n. 6) without recurrence (regardless of tumor stage) (P = 0.0006, Odds ratio = 195). These unprecedented findings clarify the pathogenic mechanism of bladder cancer recurrence and suggest that microscopically undetectable micro-foci of tumor may predispose to recurrence when associated with an inverted intratumoral T effector/Treg cell ratio.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-01-01 | Oncotarget |