Combined loss of <scp>HLA</scp> I and <scp>HLA II</scp> expression is more common in the non‐<scp>GCB</scp> type of diffuse large B cell lymphoma

Meeren, Lotte E. van der; Visser, Lydia; Diepstra, Arjan; Nijland, Marcel; Berg, Anke van den; Kluin, Philip M.

doi:10.1111/his.13445

Cited by 4 publications

(3 citation statements)

References 6 publications

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“…Non-GCB tumor cells are characterized by loss of tumor major histocompatibility complex class I [30], thus removal of the CD47 axis in this cell type may suffice to trigger phagocytosis.…”

Section: Discussionmentioning

confidence: 99%

CD47 Expression Defines Efficacy of Rituximab with CHOP in Non–Germinal Center B-cell (Non-GCB) Diffuse Large B-cell Lymphoma Patients (DLBCL), but Not in GCB DLBCL

Bouwstra

Boer

et al. 2019

Cancer Immunology Research

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“…Non-GCB tumor cells are characterized by loss of tumor major histocompatibility complex class I [30], thus removal of the CD47 axis in this cell type may suffice to trigger phagocytosis.…”

Section: Discussionmentioning

confidence: 99%

CD47 Expression Defines Efficacy of Rituximab with CHOP in Non–Germinal Center B-cell (Non-GCB) Diffuse Large B-cell Lymphoma Patients (DLBCL), but Not in GCB DLBCL

Bouwstra

Boer

et al. 2019

Cancer Immunology Research

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“…It thus remains to be determined through future studies whether distinct HLA associations will be uncovered for each of these molecularly defined DLBCL subtypes. A recent study by van der Meeren reported differential loss of HLA expression among GCB and ABC DLBCL, specifically with significantly more HLA class I and II loss in non-GCB DLBCLs than GCB DLBCLs [53]. Further evaluation of how HLA alleles influence HLA expression and lymphoma risk is thus needed.…”

Section: Future Studiesmentioning

confidence: 99%

The role of HLA variation in lymphoma aetiology and survival

et al. 2019

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Epidemiologic and laboratory evidence has consistently supported a strong inflammatory and immune component for lymphoma aetiology. These studies have consistently implicated variation in the immune gene, human leucocyte antigen (HLA), to be associated with lymphoma risk. In this review, we summarize the historical and recent evidence of HLA in both lymphoma aetiology and survival. The recent momentum in uncovering HLA associations has been propelled by the conduct of genome‐wide association studies (GWAS), which has permitted the evaluation of imputed HLA alleles in much larger sample sizes than historically feasible with allelotyping studies. Based on the culmination of smaller HLA typing studies and larger GWAS, we now recognize several HLA associations with Hodgkin (HL) and non‐Hodgkin lymphomas (NHLs) and their subtypes. Although other genetic variants have also been implicated with lymphoma risk, it is notable that HLA associations have been reported in every NHL and HL subtype evaluated to date. Both HLA class I and class II alleles have been linked with NHL and HL risk. It is notable that the associations identified are largely specific to each lymphoma subtype. However, pleiotropic HLA associations have also been observed. For example, rs10484561, which is in linkage disequilibrium with HLA‐DRB1*01:01˜DQA1*01:01˜DQB1*05:01, has been implicated in increased FL and DLBCL risk. Opposing HLA associations across subtypes have also been reported, such as for HLA‐A*01:01 which is associated with increased risk of EBV‐positive cHL but decreased risk of EBV‐negative cHL and chronic lymphocytic leukaemia/small cell lymphoma. Due to extensive linkage disequilibrium and allele/haplotypic variation across race/ethnicities, identification of causal alleles/haplotypes remains challenging. Follow‐up functional studies are needed to identify the specific immunological pathways responsible in the multifactorial aetiology of HL and NHL. Correlative studies linking HLA alleles with known molecular subtypes and HLA expression in the tumours are also needed. Finally, additional association studies investigating HLA diversity and lymphoma survival are also required to replicate initial associations reported to date.

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“…This patient cohort has been used in an earlier study. [14] The study protocol was consistent with international ethical and professional guidelines (the Declaration of Helsinki and the International Conference on Harmonization Guidelines for Good Clinical Practice). Approval for this study was obtained from the local ethics review board of the Pathology department of the University Medical Centre Groningen.…”

Section: Methodsmentioning

confidence: 99%

A super-SILAC based proteomics analysis of diffuse large B-cell lymphoma-NOS patient samples to identify new proteins that discriminate GCB and non-GCB lymphomas

et al. 2019

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Diffuse large B-cell lymphoma—not otherwise specified (DLBCL-NOS) is a large and heterogeneous subgroup of non-Hodgkin lymphoma. DLBCL can be subdivided into germinal centre B-cell like (GCB) and activated B-cell like (ABC or non-GCB) using a gene-expression based or an immunohistochemical approach. In this study we aimed to identify additional proteins that are differentially expressed between GCB and non-GCB DLBCL. A reference super-SILAC mix, including proteins of eight B-cell lymphoma cell lines, was mixed with proteins isolated from seven non-GCB DLBCL and five GCB DLBCL patient tissue samples to quantify protein levels. Protein identification and quantification was performed by LC-MS. We identified a total of 4289 proteins, with a four-fold significant difference in expression between non-GCB and GCB DLBCL for 37 proteins. Four proteins were selected for validation in the same cases and replication in an independent cohort of 47 DLBCL patients by immunohistochemistry. In the validation cohort, we observed a non-significant trend towards the same differential expression pattern as observed in the proteomics. The replication study showed significant and consistent differences for two of the proteins: expression of glomulin (GLMN) was higher in GCB DLBCL, while expression of ribosomal protein L23 (RPL23) was higher in non-GCB DLBCL. These proteins are functionally linked to important pathways involving MYC, p53 and angiogenesis. In summary, we showed increased expression of RPL23 and decreased expression of GLMN in non-GCB compared to GCB DLBCL on purified primary DLBCL patient samples and replicated these results in an independent patient cohort.

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Combined loss of HLA I and HLA II expression is more common in the non‐GCB type of diffuse large B cell lymphoma

Cited by 4 publications

References 6 publications

CD47 Expression Defines Efficacy of Rituximab with CHOP in Non–Germinal Center B-cell (Non-GCB) Diffuse Large B-cell Lymphoma Patients (DLBCL), but Not in GCB DLBCL

CD47 Expression Defines Efficacy of Rituximab with CHOP in Non–Germinal Center B-cell (Non-GCB) Diffuse Large B-cell Lymphoma Patients (DLBCL), but Not in GCB DLBCL

The role of HLA variation in lymphoma aetiology and survival

A super-SILAC based proteomics analysis of diffuse large B-cell lymphoma-NOS patient samples to identify new proteins that discriminate GCB and non-GCB lymphomas

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