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

Abstract

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.

Indolent lymphoma: follicular lymphoma and the microenvironment—insights from the microscope

“…The number and distribution of Foxp3 ϩ Treg cells and T FH cells have been reported to predict clinical prognosis in some, 54,[65][66][67] but not all, 64 studies (see Table 2 in Rimsza and Jaramillo 68 ) Even in those studies that found an effect, the results were inconsistent, with some finding that absolute numbers of Treg cells were important 54 and others 63,69,70 that the pattern (follicular, perifollicular, diffuse) was important in predicting outcome. The impact on outcome has also varied, with some studies finding that increased Treg cells were associated with a good prognosis 54,63 and others finding an association with advanced disease or a poor prognosis.…”

Clinicobiological, prognostic and therapeutic implications of the tumor microenvironment in follicular lymphoma

“…The invasive potential of FL also appeared to be related to the number of certain components of the immune infiltrate such as CD68 + macrophages and CD57 + cells. 4 Although the histological grade was not significantly associated with the FL patients' survival, this study revealed a statistically significant lesser infiltration of CD68 + macrophages but also a greater infiltration of CD57 + cells in patients with low-grade (1-2) FL as compared to in patients with grade 3 FL. The apparently paradoxical observation that patients with low-grade FL have more extensive tumor cell trafficking among FL follicles during clonal expansion 18,19 appears in agreement with these results, since patients with grade 1 and 2 FL show a significantly higher percentage of B symptoms and bone marrow involvement than those with grade 3.…”

“…6,7 A high level of CD4 + T lymphocytes was significantly associated with overall survival in some cases, 6 but others studies found no effect. 7 The number of CD8 + T lymphocytes was found to be associated with overall survival and disease-free survival 4,8 but with discrepancies between the studies. FOXP3…”

“…7 In a large and representative cohort of FL patients, significant differences were found in host immune response between patients whose disease was indolent and those whose lymphoma had an aggressive clinical course. 4 The group of FL patients with indolent disease had an immunosurveillance pattern of immune response with more infiltrated T lymphocytes and macrophages in the microenvironment of the tumor, a low performance status, absence of B symptoms, absence of bone marrow involvement, low number of nodal sites (≤4), low Ann Arbor stage and low-risk FLIPI score (Figure 2). The invasive potential of FL also appeared to be related to the number of certain components of the immune infiltrate such as CD68 + macrophages and CD57 + cells.…”

“…4 The 10 and FOXP3 + regulatory T cells. 6,7 A high level of CD4 + T lymphocytes was significantly associated with overall survival in some cases, 6 but others studies found no effect.…”