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Immunohistochemical Patterns of Reactive Microenvironment Are Associated With Clinicobiologic Behavior in Follicular Lymphoma Patients

Tomás Álvaro, Marylène Lejeune, Maria-Teresa Salvadó, Carlos Lopez, Joaquín Jaén, Ramón Bosch, Lluis E. Pons

From the Department of Pathology, Hospital Verge de la Cinta, Tortosa, Spain

Address reprint requests to Tomás Álvaro-Naranjo, MD, PhD, Department of Pathology, Hospital de Tortosa Verge de la Cinta, C/Esplanetes No. 14, 43500 Tortosa, Spain; e-mail: talvaro.htvc.ics{at}gencat.net

PURPOSE: Recent molecular data have suggested that non-neoplastic cells are powerful modulators that may confer a selective advantage or disadvantage on the outcome of follicular lymphoma (FL) patients.

PATIENTS AND METHODS: The prevalence of the principal inflammatory and immune-infiltrated cells was measured immunohistochemically in the tissue of 211 FL patients, and associations were sought with their traditional clinicobiologic characteristics.

RESULTS: Our results confirmed the presence of a large number of T lymphocytes (CD4⁺ and CD8⁺) and CD57⁺ cells and, at a moderate level, the presence of TIA-1⁺ cytotoxic cells, CD68⁺ macrophages, CD123⁺ plasmacytoid cells, and FOXP3⁺ regulatory T cells among the pool of non-neoplastic cells. In addition to the conventional clinical variables, univariate analysis identified a low level of infiltrated CD8⁺ T lymphocytes as a significantly negative prognostic factor of overall survival. The following significant differences in the abundance of cells of specific and nonspecific immunity were observed in relation to the clinicobiologic features of FL: (1) a reactive microenvironment mainly made up of T lymphocytes and macrophages was significantly associated with a favorable clinical behavior of FL patients; and (2) a reactive microenvironment infiltrated predominantly by CD57⁺ T cells was associated with a significantly higher frequency of adverse clinicobiologic manifestations such as "B" symptoms and bone marrow involvement.

CONCLUSION: Our results demonstrate the existence of two specific patterns in the reactive microenvironment of FL, an immunosurveillance pattern (T lymphocytes and macrophages) and an immune-escape pattern (CD57⁺ T cells), that were directly associated with the clinicobiologic features of these patients.

Supported by Grants No. G03/179 and FIS 05/0474 from the Ministerio de Ciencia y Tecnología, Spain.

Some results were presented at XXII Jornades Mèdiques i Ciències de la Salut de les Terres de L’Ebre, February 24–25, 2006, Tortosa, Spain.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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