From brain to testis: immune escape and clonal selection in a B cell lymphoma with selective out-growth in two immune sanctuariesy

Booman, Marije; Douwes, Jenny; Legdeur, Marie-Cecile; Baarlen, Joop van; Schuuring, Ed; Kluin, Philip M.

doi:10.3324/haematol.11421

Cited by 19 publications

(11 citation statements)

References 23 publications

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“…The extranodal large B‐cell lymphoma entities include CNS DLBCL; primary testicular DLBCL; primary cutaneous DLBCL, leg type; and IVLBCL. These are rare and aggressive non‐Hodgkin lymphomas and affected patients frequently have the MYD88 L265P mutation and a high risk for secondary CNS relapse, even in the era of rituximab . Recent genetic analyses revealed frequent 9p24.1/PD‐L1 (CD274)/PD‐L2 (PDCD1LG2) copy number alterations and less frequently PD‐L1 or PD‐L2 translocations that are associated with increased expression of PD‐L1 on their tumor cells .…”

Section: Discussionmentioning

confidence: 99%

“…Some of these variants have been pointed out in the current classification because of unique clinical characteristics and a predilection for specific anatomic sites, which often reflects an underlying biological distinctiveness. These include primary DLBCL of the central nervous system (CNS DLBCL); primary testicular DLBCL; primary cutaneous DLBCL, leg type; and intravascular large B‐cell lymphoma (IVLBCL), which have a propensity for exclusively affecting the extranodal sites and a higher risk of secondary CNS relapse during their clinical courses . However, the reasons for these peculiar biological behaviors remain unclear.…”

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confidence: 99%

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Immune evasion‐related extranodal large B‐cell lymphoma: A report of six patients with neoplastic PD‐L1‐positive extranodal diffuse large B‐cell lymphoma

Suzuki

Sakakibara

Shimada

et al. 2019

Pathology International

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We identified six patients with Epstein-Barr virus (EBV)-negative extranodal diffuse large B-cell lymphoma (DLBCL) and immunohistochemical expression of PD-L1 on their tumor cells by examining 283 DLBCL cases with the PD-L1 SP142 clone between 2015 and 2017. They consisted of two men and four women with a median age of 71 years, and were examined in an autopsy (n ¼ 1) and biopsies from the adrenal gland (n ¼ 2), skin (n ¼ 1), pelvic cavity (n ¼ 1), and kidney (n ¼ 1). All showed a monomorphic population of large transformed B-cells leading to diagnoses of DLBCL with two intravascular large B-cell lymphoma (IVLBCL) and one de novo CD5þ type and were featured by an invariable immunephenotype: CD3-, CD20þ, BCL-2þ, and MUM1þ. In addition, CD5 and CD10 were each detected in one case. All cases expressed PD-L1 on >10% to >90% of tumor cells, which was confirmed with two other PD-L1 antibodies (E1J2J and 28-8). Three untreated patients had a rapid, lethal clinical course within 7 months after diagnosis; while, the remaining three achieved complete remission after treatment and were alive at the last follow-up. We suggest immune evasion-related extranodal large B-cell lymphoma should be recognized beyond the currently identified entities of IVLBCL and de novo CD5þ DLBCL. K E Y W O R D S de novo CD5þ diffuse large B-cell lymphoma, extranodal diffuse large B-cell lymphoma, immune evasion, intravascular large B-cell lymphoma, neoplastic PD-L1 expression Pathology

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Immune evasion‐related extranodal large B‐cell lymphoma: A report of six patients with neoplastic PD‐L1‐positive extranodal diffuse large B‐cell lymphoma

Suzuki

Sakakibara

Shimada

et al. 2019

Pathology International

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“…Primary IP‐DLBCLs share many features including frequent dissemination to other immune‐privileged sites 10, 28–32. This suggests that these lymphomas share important biological features such as similar expression of adhesion molecules, homing receptors or chemokines and their receptors 33–35.…”

Section: Discussionmentioning

confidence: 99%

Genomic alterations and gene expression in primary diffuse large B‐cell lymphomas of immune‐privileged sites: the importance of apoptosis and immunomodulatory pathways

Booman

Szuhai

Rosenwald

et al. 2008

The Journal of Pathology

100

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Primary diffuse large B-cell lymphomas of different immune-privileged sites (IP-DLBCLs) share many clinical and biological features, such as a relatively poor prognosis, preferential dissemination to other immune-privileged sites, and deletion of the HLA region, which suggests that IP-DLBCL represents a separate entity. To further investigate the nature of IP-DLBCL, we investigated site-specific genomic aberrations in 16 testicular, nine central nervous system (CNS), and 15 nodal DLBCLs using array CGH. We also determined minimal common regions of gain and loss. Using robust algorithms including multiple testing procedures and the ACE-it script, which is specifically designed for this task, the array CGH data were combined with gene expression data to explore pathways deregulated by chromosomal aberrations. Loss of 6p21.32-p25.3, including the HLA genes, was associated with both types of IP-DLBCL, whereas gain of 2p16.1-p25.3 was associated with nodal DLBCL. Gain of 12q15-q21.1 and 12q24.32-q24.33 was associated with CNS DLBCL and gain of 19q13.12-q13.43 with testicular DLBCL. Analysis of candidate genes in site-specific regions and minimal common regions revealed two major groups of genes: one involved in the immune response, including regulation of HLA expression, and the other involved in apoptosis, including the p53 pathway. Many of these genes were also involved in homozygous deletions or high-level gains. The presence of both shared and site-specific aberrations in CNS and testicular DLBCLs underlines the concept of IP-DLBCL but also indicates that IP-DLBCLs of the CNS and testis do not form a single entity. The observed aberrations emphasize the importance of the deregulation of anti-tumour immune response and apoptosis pathways.

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“…43 There is evidence from single reports on an original PCNSL and its relapse that both tumors shared a common ancestor, presumably a premalignant precursor cell. 44,45 IGH gene analysis identified the same V, D and J gene segments, and almost identical CDR3 sequences, in cells of the primary and recurrent tumor, respectively. While they shared several mutations in their V gene segments, each tumor-related sequence was characterized by unique mutations.…”

Section: Biology Of Pcnslmentioning

confidence: 99%

Modern concepts in the biology, diagnosis, differential diagnosis and treatment of primary central nervous system lymphoma

et al. 2011

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From brain to testis: immune escape and clonal selection in a B cell lymphoma with selective out-growth in two immune sanctuariesy

Cited by 19 publications

References 23 publications

Immune evasion‐related extranodal large B‐cell lymphoma: A report of six patients with neoplastic PD‐L1‐positive extranodal diffuse large B‐cell lymphoma

Immune evasion‐related extranodal large B‐cell lymphoma: A report of six patients with neoplastic PD‐L1‐positive extranodal diffuse large B‐cell lymphoma

Genomic alterations and gene expression in primary diffuse large B‐cell lymphomas of immune‐privileged sites: the importance of apoptosis and immunomodulatory pathways

Modern concepts in the biology, diagnosis, differential diagnosis and treatment of primary central nervous system lymphoma

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