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^*

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.

Keywords:

• Lymphoma and Hodgkin disease
• lymphocytes
• T-cell mediated immunity

Acknowledgements

The authors wish to thank Gloria Ercilla, Isabel Martín and María Teresa González (University Hospital of Salamanca, Spain) for their technical support. The authors are also grateful to all the members of the HOLCYL group and the patients who participated in this study. This work was partially supported by the Red Temática de Investigación Cooperativa en Cáncer RD12/0036/0069, subprograma Tumores Hematológicos, ‘Programa INNOCAMPUS de la Universidad de Salamanca’, and a grant from the ‘Health Council of Castilla y León [GRS265/A/08]’.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2016.1239263.