Higher infiltration of intratumoral CD25+ FOXP3+ lymphocytes correlates with a favorable prognosis in patients with diffuse large B-cell lymphoma

Abstract

Regulatory T-cells (Tregs) play an important role in cancer immunity but their prognostic impact is controversial in diffuse large B-cell lymphoma (DLBCL). Intratumoral Tregs in DLBCL (n = 70) were evaluated by double-stained CD25 and FOXP3 lymphocytes in formalin-fixed paraffin-embedded tissues, and correlated with clinicopathologic features. We found that increased numbers of intratumoral FOXP3+ lymphocytes (>2.4/HPF) and CD25 + FOXP3+ lymphocytes (>0.8/HPF) are favorable prognosticators (p = .004 and p < .001, respectively) in DLBCL patients, along with age <70 years, stage I–II disease, normal serum LDH level and low IPI scores (p < .001, .002, .002, and <.001, respectively). On multivariate analyses, a higher number of CD25 + FOXP3+ lymphocytes retained prognostic significance (p = .040). Interestingly, higher Treg infiltration correlated with increased infiltration by cytotoxic T-lymphocytes (γ = 0.294, p = .038) and nodal location (γ = 0.390, p = .004), but not with infiltration by CD123+ plasmacytoid dendritic cells, which were reported to induce Tregs with immune tolerance. Therefore, congruent with literature meta-analyses, higher intratumoral CD25 + FOXP3+ lymphocytes have a beneficial impact on DLBCL.

Keywords:

• Diffuse large B-cell lymphoma
• regulatory T-cells (Tregs)
• CD25
• FOXP3
• prognosis

Acknowledgements

We are grateful for the support from the Human Biobank, Research Center of Clinical Medicine, National Cheng Kung University Hospital.

Author contributions

Chen Chang: performance of analysis and drafting the article. Ya-Ping Chen and Tsai-Yu Chen: acquisition and analysis of clinical data. L. Jeffrey Medeiros: data analysis and critical review and revision of the draft. Kung-Chao Chang: design, analysis and interpretation of data and revision of the draft.

Disclosure statement

The authors reported no potential conflicts of interest.

Additional information

Funding

This study is supported by grants from the Ministry of Science and Technology, Taiwan (MOST 106-2320-B-006-037-MY3 and 109-2320-B-006-045-MY3) to Dr. K.C. Chang.