Human Cancer Biology Pattern of CD14þ Follicular Dendritic Cells and PD1þ T Cells Independently Predicts Time to Transformation in Follicular Lymphoma

نویسندگان

  • Jacob P. Smeltzer
  • Jason M. Jones
  • Steven C. Ziesmer
  • Deanna M. Grote
  • Bing Xiu
  • Kay M. Ristow
  • Zhi Zhang
  • Grzegorz S. Nowakowski
  • Andrew L. Feldman
  • James R. Cerhan
  • Anne J. Novak
  • Stephen M. Ansell
چکیده

Purpose: Transformation of follicular lymphoma is a critical event associated with a poor prognosis. The role of the tumor microenvironment in previous transformation studies has yielded conflicting results. Experimental Design: To define cell subtypes associated with transformation, we examined tissue specimens at diagnosis from patients with follicular lymphoma that later transformed and, 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 andmulticolor IHC. Results: Of note, 58 patients were analyzed with median TTT of 4.7 years. The pattern of PD1þ and CD14þ cells rather than the quantity of cells was predictive of clinical outcomes. On multivariate analysis, including the follicular lymphoma international prognostic index score, CD14þ cells localized in the follicle were associatedwith a shorter TTT (HR, 3.0;P1⁄40.004). PD1þ cellswithdiffuse stainingwere associatedwith a shorter TTT (HR, 1.9; P1⁄4 0.045) and inferior OS (HR, 2.5; P1⁄4 0.012).Multicolor IHC and flow cytometry identified CD14þ cells as follicular dendritic cells (FDC), whereas PD1þ cells represented two separate populations, TFH and exhausted T cells. Conclusion: These results identify the presence of PD1þ T cells and CD14þ FDC as independent predictors of transformation in follicular lymphoma. Clin Cancer Res; 20(11); 2862–72. 2014 AACR.

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تاریخ انتشار 2014