title: Tumor infiltrating T lymphocytes expressing FoxP3, CCR7 or PD-1 predict the outcome of prostate cancer patients subjected to salvage radiotherapy after biochemical relapse.
abstract: Tumor immunologic microenvironment is strongly involved in tumor progression and the presence of tumor infiltrating lymphocytes (TIL) with different phenotypes has been demonstrated to be of prognostic relevance in different malignancies. We investigated whether TIL infiltration of tumor tissues could also predict the outcome of prostate cancer patients. To this end, we carried out a retrospective analysis correlating the outcome of locally advanced prostate cancer patients undergone salvage radiotherapy upon relapse after radical surgery with the infiltration by different TIL populations. Twenty-two patients with resectable prostate cancer, with a mean age of 67 (+/-3.93) years, who received salvage radiotherapy with a mean of 69.66 (+/- 3.178) Gy in 8 weeks, between June 1999 and January 2009 and with a median follow up of 123 (+/- 55.82) months, were enrolled in this study. We evaluated, by immunohistochemistry, the intratumoral (t) and peripheral stroma (p) infiltration by CD45, CD3, CD4, CD8, CCR7, FoxP3 or PD-1-positive cells on tumor samples taken at the diagnosis (d) and relapse times (R). We correlated these variables with patients' biochemical progression free survival (bPFS), post-radiotherapy progression free survival (PFS), and overall survival (OS). Substantial changes in the rate of TIL subsets were found between the first and the second biopsy with progressive increase in CD4, CCR7, FoxP3, PD-1+cells. Our analysis revealed that higher CD8p,R+and lower PD-1R+TIL scores correlated to a longer bPFS. Higher CD8p,R+and CCR7t,R+TIL scores and lower CD45p,R+and FoxP3p,R+TIL scores correlated to a prolonged PFS and OS. These results suggest that the immunological microenvironment of primary tumor is strictly correlated with patient outcome and provide the rationale for immunological treatment of prostate cancer.
authors: a Radiotherapy Unit, Department of Oncology , Siena University School of Medicine , Italy.|b Tuscany Tumor Institute (ITT) , Firenze , Italy.
authors: Valerio
authors: V
authors: Nardone
authors: c Medical Oncology Unit, Department of Clinical and Experimental Medicine , "Magna Graecia" University of Catanzaro , Catanzaro , Italy.
authors: Cirino
authors: C
authors: Botta
authors: d Department of Biochemistry , Biophysics and General Pathology, Second University of Naples , Naples , Italy.
authors: Michele
authors: M
authors: Caraglia
authors: a Radiotherapy Unit, Department of Oncology , Siena University School of Medicine , Italy.
authors: Elodia Claudia
authors: EC
authors: Martino
authors: e Section of Pathology, Department of Medical Biotechnology , University of Siena , Siena , Italy.
authors: Maria Raffaella
authors: MR
authors: Ambrosio
authors: a Radiotherapy Unit, Department of Oncology , Siena University School of Medicine , Italy.|b Tuscany Tumor Institute (ITT) , Firenze , Italy.
authors: Tommaso
authors: T
authors: Carfagno
authors: a Radiotherapy Unit, Department of Oncology , Siena University School of Medicine , Italy.|b Tuscany Tumor Institute (ITT) , Firenze , Italy.
authors: Paolo
authors: P
authors: Tini
authors: a Radiotherapy Unit, Department of Oncology , Siena University School of Medicine , Italy.|b Tuscany Tumor Institute (ITT) , Firenze , Italy.
authors: Leonardo
authors: L
authors: Semeraro
authors: d Department of Biochemistry , Biophysics and General Pathology, Second University of Naples , Naples , Italy.
authors: Gabriella
authors: G
authors: Misso
authors: d Department of Biochemistry , Biophysics and General Pathology, Second University of Naples , Naples , Italy.
authors: Anna
authors: A
authors: Grimaldi
authors: d Department of Biochemistry , Biophysics and General Pathology, Second University of Naples , Naples , Italy.
authors: Mariarosaria
authors: M
authors: Boccellino
authors: f Urogynechological Department , INT Fondazione "G. Pascale " Naples , Italy.
authors: Gaetano
authors: G
authors: Facchini
authors: g Department of Medical Oncology , National Cancer Institute , Aviano (PN ) Italy.
authors: Massimiliano
authors: M
authors: Berretta
authors: a Radiotherapy Unit, Department of Oncology , Siena University School of Medicine , Italy.|b Tuscany Tumor Institute (ITT) , Firenze , Italy.
authors: Gianluca
authors: G
authors: Vischi
authors: e Section of Pathology, Department of Medical Biotechnology , University of Siena , Siena , Italy.|h Pathology Unit , Ospedale di Circolo di Busto Arsizio (VA) Italy.
authors: Bruno Jim
authors: BJ
authors: Rocca
authors: e Section of Pathology, Department of Medical Biotechnology , University of Siena , Siena , Italy.
authors: Aurora
authors: A
authors: Barone
authors: c Medical Oncology Unit, Department of Clinical and Experimental Medicine , "Magna Graecia" University of Catanzaro , Catanzaro , Italy.
authors: Pierfrancesco
authors: P
authors: Tassone
authors: c Medical Oncology Unit, Department of Clinical and Experimental Medicine , "Magna Graecia" University of Catanzaro , Catanzaro , Italy.
authors: Pierosandro
authors: P
authors: Tagliaferri
authors: e Section of Pathology, Department of Medical Biotechnology , University of Siena , Siena , Italy.
authors: Maria Teresa
authors: MT
authors: Del Vecchio
authors: a Radiotherapy Unit, Department of Oncology , Siena University School of Medicine , Italy.|b Tuscany Tumor Institute (ITT) , Firenze , Italy.
authors: Luigi
authors: L
authors: Pirtoli
authors: a Radiotherapy Unit, Department of Oncology , Siena University School of Medicine , Italy.|b Tuscany Tumor Institute (ITT) , Firenze , Italy.
authors: Pierpaolo
authors: P
authors: Correale
mesh_terms: D000368:Aged; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy*; D054400:Receptors, CCR7 / Q000096:biosynthesis / Q000276:immunology*; D012008:Recurrence; D016879:Salvage Therapy / Q000379:methods*; D059016:Tumor Microenvironment
chemical_list: C515370:CCR7 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D054400:Receptors, CCR7
keywords: Chemokyne Receptor 7; FoxP3; PD-1; T regulators lymphocytes; disease-free survival; overall survival; prognosis; prostate cancer; radiotherapy; tumor infiltrating lymphocytes