title: The number of tumor infiltrating T-cell subsets in lymph nodes from patients with Hodgkin lymphoma is associated with the outcome after first line ABVD therapy<sup/>.
abstract: Prognostic factors in Hodgkin lymphoma (HL) still fail to accurately identify high-risk patients. Tumor microenvironment in HL is a current focus of research for risk definition but few studies have focused on infiltrating lymphocytes. Here, we analyzed the number of tumor infiltrating lymphocytes by flow cytometry in diagnostic biopsies from 96 HL homogeneously treated patients with ABVD with or without radiotherapy. Most lymph node cells were lymphocytes (90 ± 17), with a median T/B/NK distribution of 74%/26%/0.7%, and CD4+T-cell predominance. The amount of CD19+B cells, and NK cells did not show association with disease features. However, high numbers of CD8+and CD4+cells were associated with better and poorer outcomes, respectively. Patients with ≥15% cytotoxic CD8+cells among the total cell population had a longer 10-year freedom from treatment failure (FFTF) (93% vs. 73%, p=.04). In turn, cases with ≥75% of CD4+infiltrating cells showed a significantly decreased FFTF (73% vs. 96%, p=.021). Consequently, CD4/CD8 ratio ≥5 associated with a poorer 10-year FFTF (69.5% vs. 94%, p=.02). This deleterious effect was particularly prominent in advanced disease (n = 58, p=.01). In multivariate analysis, a CD4/CD8 ratio ≥5 was the only independent variable to predict for treatment failure (HR = 4.5, 95% confidence interval, 1.2-16.8). In conclusion, our study shows that high CD4+and low CD8+T-cells infiltrates of tumor specimens associate with poor prognosis in HL patients, and CD4/CD8 ratio might be potentially useful for tailoring therapy.
authors.affiliation: a IBMCC (USAL-CSIC) , Hospital Universitario de Salamanca-IBSAL , Salamanca , Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Alonso-Álvarez
authors.affiliation: a IBMCC (USAL-CSIC) , Hospital Universitario de Salamanca-IBSAL , Salamanca , Spain.
authors.forename: Maria Belén
authors.initials: MB
authors.lastname: Vidriales
authors.affiliation: a IBMCC (USAL-CSIC) , Hospital Universitario de Salamanca-IBSAL , Salamanca , Spain.
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Caballero
authors.affiliation: a IBMCC (USAL-CSIC) , Hospital Universitario de Salamanca-IBSAL , Salamanca , Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Blanco
authors.affiliation: a IBMCC (USAL-CSIC) , Hospital Universitario de Salamanca-IBSAL , Salamanca , Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Puig
authors.affiliation: a IBMCC (USAL-CSIC) , Hospital Universitario de Salamanca-IBSAL , Salamanca , Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Martin
authors.affiliation: b Hospital Clínico Universitario de Valladolid , Valladolid , Spain.
authors.forename: Maria Jesús
authors.initials: MJ
authors.lastname: Peñarrubia
authors.affiliation: b Hospital Clínico Universitario de Valladolid , Valladolid , Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Zato
authors.affiliation: c Hospital Camino de Santiago de Ponferrada , Ponferrada , Spain.
authors.forename: Josefina
authors.initials: J
authors.lastname: Galende
authors.affiliation: d Hospital N.S. de Sonsoles de Ávila , Ávila , Spain.
authors.forename: Abelardo
authors.initials: A
authors.lastname: Bárez
authors.affiliation: a IBMCC (USAL-CSIC) , Hospital Universitario de Salamanca-IBSAL , Salamanca , Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Alcoceba
authors.affiliation: a IBMCC (USAL-CSIC) , Hospital Universitario de Salamanca-IBSAL , Salamanca , Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfão
authors.affiliation: a IBMCC (USAL-CSIC) , Hospital Universitario de Salamanca-IBSAL , Salamanca , Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.affiliation: a IBMCC (USAL-CSIC) , Hospital Universitario de Salamanca-IBSAL , Salamanca , Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Sanz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers; D001761:Bleomycin / Q000009:adverse effects / Q000627:therapeutic use; D016516:CD4-CD8 Ratio; D002648:Child; D003606:Dacarbazine / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality* / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D012372:ROC Curve; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D014747:Vinblastine / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001761:Bleomycin; D014747:Vinblastine; D003606:Dacarbazine; D004317:Doxorubicin
keywords: Lymphoma and Hodgkin disease; T-cell mediated immunity; lymphocytes