Ferreri, Andrés J M
Mayo Clinic
IRCCS San Raffaele Scientific Institute.
Citations 2
Prognostic gene expression and microRNA profiling signatures and genetic alterations in primary testicular diffuse large B-cell lymphoma
Young, Ken H. , Jia, Youchao, Tzankov, Alexandar , Go, Heounjeong , Li, Ling , Zhai, Qiong-Li , Perry, Anamarija M. , Wang, Shi , Wang, Xiaoxiao , Chiu, April , Xu, Mina L. , Visco, Carlo , Yuan, Alyssa F. , Miao, Yi , Li, Jianyong , Shuai, Wen , Wang, Bangchen , Pan, Zenggang , Chen, Weina , Zhang, Shanxiang , Sohani, Aliyah R. , Ferreri, Andrés J.M. , Xu, Bing , Young, Ken H , Tzankov, Alexandar , Go, Heounjeong , Xu, Mina , Dybkaer, Karen , Withers, Henry , Li, Jianyong , Bhagat, Govind , Chen, Weina , Møller, Michael Boe , Zhan, Fenghuang , Sohani, Aliyah , Ferreri, Andrés J M , Xu, Bing , Li, Yong , Wang, Bangchen , Shi, Wenyu , Xu‐Monette, Zijun Y. , Ponzoni, Maurilio , Wang, Yafei , Dybkær, Karen , Long, Mark D. , Macias, Everardo , Bhagat, Govind , Zu, Youli , Choi, William, Montes‐Moreno, Santiago , Krieken, J. Han van , Møller, Michael , Zhan, Fenghuang , Parsons, Benjamin M. , Hsi, Eric D. , Abramson, Jeremy S. , Li, Yong
No container title available | January 6, 2025 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a rare and aggressive lymphoma with molecular heterogeneity not well characterize. In this study, we performed next-generation sequencing analysis for a large number of DNA and RNA samples from patients with PT-DLBCL. DNA sequencing analysis identified ≥ 3 chromosomes with copy number variations (CNVs) and microsatellite instability as prognostic biomarkers, rather than MYD88 mutations and genetic subtypes. Remarkably, targeted RNA-seq analysis in 195 patients revealed that TP53 mutations with a ≥ 40% variant allele frequency had significantly adverse prognostic impact, and that a 150-gene expression signature subdivided PT-DLBCL into two distinct clusters, termed as testicular lymphoma tumor (TLT) and microenvironment (ME) subtypes. The TLT subtype featured upregulation of genes involved in B-cell receptor signaling, cell cycle, DNA damage and repair, higher frequencies of CNVs and MYD88 mutations, elder ages, larger tumor sizes, and significantly poorer survival. Genomic microRNA profiling analysis identified significantly differentially expressed microRNAs between 113 PT-DLBCL and 180 systemic DLBCL patients, and further subdivided the PT-DLBCL cohort by microRNA signatures. The subcohort with upregulation of 16 microRNAs associated with PT-DLBCL and testicular tissue expression had significantly better survival. This study revealed characteristic genetic, gene expression, and microRNA profiles and heterogeneity in PT-DLBCL.
Tumor-Infiltrating Normal B Cells Revealed by Immunoglobulin Repertoire Clonotype Analysis Are Highly Prognostic and Crucial for Antitumor Immune Responses in DLBCL
Xu‐Monette, Zijun Y. , Li, Yong , Snyder, Thomas M. , Yu, Tiantian , Lu, Tingxun , Tzankov, Alexandar , Visco, Carlo , Bhagat, Govind , Qian, Wenbin , Dybkær, Karen , Chiu, April , Tam, Wayne , Zu, Youli , Hagemeister, Fredrick B., Wang, Yingjun , Ferreri, Andrés J.M. , Møller, Michael , Parsons, Benjamin M. , Fan, Xiangshan , Au, Qingyan , Zhang, Mingzhi , Shaughnessy, John D. , Xu, Bing , Young, Ken H. , Snyder, Thomas , Lu, Tingxun , Hsi, Eric D , Hagemeister, Fredrick B , Wang, Yingjun , Go, Heounjeong , Ponzoni, Maurilio , Ferreri, Andrés J M , Møller, Michael Boe , Parsons, Benjamin M , Fan, Xiangshan , van Krieken, J Han , Piris, Miguel , Winter, Jane N , Au, Qingyan , Kirsch, Ilan , Zhang, Mingzhi , Shaughnessy, John , Xu, Bing , Young, Ken H , Tzankov, Alexandar , Dybkaer, Karen , Li, Yong , Bhagat, Govind , Zu, Youli , Xu-Monette, Zijun Y , Hsi, Eric D. , Go, Heounjeong , Ponzoni, Maurilio , Krieken, J. Han van , Piris, Miguel Á. , Winter, Jane N. , Kirsch, Ilan R.
Clinical Cancer Research | September 20, 2023 | Volume: 29 | Issue: 23 | Pages: 4808-4821
Abstract Purpose: Tumor-infiltrating B lymphocytes (TIL-B) have demonstrated prognostic and predictive significance in solid cancers. In this study, we aimed to distinguish TIL-Bs from malignant B-cells in diffuse large B-cell lymphoma (DLBCL) and determine the clinical and biological significance. Experimental Design: A total of 269 patients with de novo DLBCL from the International DLBCL R-CHOP Consortium Program were studied. Ultra-deep sequencing of the immunoglobulin genes was performed to determine B-cell clonotypes. The frequencies and numbers of TIL-B clonotypes in individual repertoires were correlated with patient survival, gene expression profiling (GEP) data, and frequencies of DLBCL-infiltrating immune cells quantified by fluorescent multiplex IHC at single-cell resolution. Results: TIL-B abundance, evaluated by frequencies of normal B-cell clonotypes in the immunoglobulin repertoires, remarkably showed positive associations with significantly better survival of patients in our sequenced cohorts. DLBCLs with high versus low TIL-B abundance displayed distinct GEP signatures, increased pre-memory B-cell state and naïve CD4 T-cell state fractions, and higher CD4+ T-cell infiltration. TIL-B frequency, as a new biomarker in DLBCL, outperformed the germinal center (GC) B-cell–like/activated B-cell–like classification and TIL-T frequency. The identified TIL-B–high GEP signature, including genes upregulated during T-dependent B-cell activation and those highly expressed in normal GC B cells and T cells, showed significant favorable prognostic effects in several external validation cohorts. Conclusions: TIL-B frequency is a significant prognostic factor in DLBCL and plays a crucial role in antitumor immune responses. This study provides novel insights into the prognostic determinants in DLBCL and TIL-B functions with important therapeutic implications.