Dynamic change of soluble interleukin-2 receptor distinguished molecular heterogeneity and microenvironment alterations in diffuse large B-cell lymphoma

Abstract

Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with variable clinical outcomes and prediction of prognosis remains important for long-term remission. We performed serial serum soluble interleukin-2 receptor (sIL-2R) measurement pretreatment and before each cycle of the treatment in 599 patients with de novo DLBCL. Genomic and transcriptomic features were analyzed by 223 DNA- and 227 RNA-sequencing, respectively. Applying the cut-off value to sIL-2R pretreatment and cycle 2 (C2) level, patients were classified into FINE subtype (pretreatment low level) with good prognosis, RES subtype (pretreatment high level and C2 low level) with intermediate prognosis, and RET subtype (pretreatment high level and C2 high level) with poor prognosis, independent of International Prognostic Index. In “others” genetic subtype, dynamic change of sIL-2R showed prognostic significance and genetic features. Compared with FINE subtype, RES subtype had increased ARID1A and MYD88 mutations, and RET subtype had increased KMT2D, LYN and SOCS1 mutations. RES and RET subtypes showed significant enrichment in oncogenic pathways, such as ERK, NF-κB, JAK-STAT, and immune-associated pathways. As for tumor microenvironment, RES subtype exhibited increased recruiting activity of CD8 + T, T helper 1, and natural killer cells, and RET subtype with increased recruiting activity of CD4 + T and regulatory T cells in silico. There was a positive correlation between transcripts of IL-2R and immune checkpoint expressions including PD-1 and CTLA-4. Our findings identified that dynamic change of sIL-2R, with this simple and easy detection method in peripheral blood, had long-term prognostic effect and specific relation to microenvironment alterations in DLBCL.

The Impact of Tumor Hypoxia Modulation on sIL-2R Levels in Newly Diagnosed Diffuse Large B Cell Lymphoma (DLBCL) Patients Undergoing Chemotherapy: A Randomized Clinical Trial

“…The role of nicotinamide in reducing sIL-2R levels may be elucidated by an in vitro study conducted by Hu et al [ 25 ] where mice with breast cancer treated with nicotinamide displayed an improved T-cell immune profile [ 25 ]. Additionally, a study by Huo et al [ 26 ] indicated a significant decrease in sIL-2R levels in DLBCL patients, which was directly linked to a more favorable prognosis in terms of both progression-free survival (PFS) and overall survival (OS) [ 26 ].…”

Lymphoproliferative disease: could they be localized in the pancreas?

“…Наиболее часто ПЛПЖ поражает головку поджелудочной железы (33,3%), за которой следуют тело и хвост (33,3%). Вторичная НЛХ поджелудочной железы обычно поражает всю поджелудочную железу (42,6%) [6,7].…”

α-KG inhibits tumor growth of diffuse large B-cell lymphoma by inducing ROS and TP53-mediated ferroptosis

“…However, approximately 40% of cases progress to relapsed/refractory DLBCL [ 3 ]. Recently, molecular heterogeneity of DLBCL has been identified as a major factor interfering with clinical treatment responses [ 4 ], especially in double-hit lymphoma (DHL) and triple-hit lymphoma (THL) [ 5 , 6 ]. Investigation of new therapeutic strategies is an urgent need to guide clinical practice.…”