Follicular lymphoma is the second most common type of non-Hodgkin lymphoma (NHL). With a median overall survival (OS) of nearly 10 years, follicular lymphoma exhibits periods of disease remission and stability punctuated by intermittent relapses. However, some patients undergo histologic transformation to an aggressive lymphoma. Histologic transformation is often associated with rapid progression, refractoriness to treatment, and an overall dismal prognosis.
In previous transformation studies, the role of the tumor microenvironment has yielded conflicting results. A recent study in Clinical Cancer Research completed by Mayo Clinic researchers, first author Stephen Ansell, M.D., Ph.D., examined tissue specimens at diagnosis from patients with follicular lymphoma that later transformed to define cell subtypes associated with transformation.
Using immunohistochemistry (IHC), stained for CD68, CD11c, CD21, CXCL13, FOXP3, PD1, and CD14, cell content and the pattern of expression were evaluated. Those identified as significantly associated with time to transformation (TTT) and overall survival (OS) were further characterized by flow cytometry and multicolor IHC.
During the study, 58 patients were analyzed with median TTT of 4.7 years. The pattern of PD1(+) and CD14(+) cells rather than the quantity of cells was predictive of clinical outcomes. On multivariate analysis, including the follicular lymphoma international prognostic index score, CD14(+) cells localized in the follicle were associated with a shorter TTT. PD1(+) cells with diffuse staining were associated with a shorter TTT and inferior OS. Multicolor IHC and flow cytometry identified CD14(+) cells as follicular dendritic cells (FDC), whereas PD1(+) cells represented two separate populations, TFH and exhausted T cells.
Based on these results, the presence of PD1(+) T cells and CD14(+) FDC are independent predictors of transformation in follicular lymphoma.