ORCID Profile
0000-0002-5790-8584
Current Organisation
University College London
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Publisher: BMJ
Date: 10-2017
Publisher: Oxford University Press (OUP)
Date: 09-02-2016
DOI: 10.1093/HMG/DDW027
Publisher: Oxford University Press (OUP)
Date: 28-09-2018
Publisher: American Association for Cancer Research (AACR)
Date: 15-07-2018
DOI: 10.1158/0008-5472.CAN-17-2900
Abstract: A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of “heterozygote advantage” regarding the role of HLA and NHL, whereby HLA ersity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06–1.60 OR MZL = 1.45, 95% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24–3.55 OR MZL = 2.10, 95% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend & 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene ersity reduces risk for non-Hodgkin lymphoma. Cancer Res 78(14) 4086–96. ©2018 AACR.
Publisher: Springer Science and Business Media LLC
Date: 22-05-2020
DOI: 10.1038/S43018-020-0066-Y
Abstract: Tumour mutational burden (TMB) predicts immunotherapy outcome in non-small cell lung cancer (NSCLC), consistent with immune recognition of tumour neoantigens. However, persistent antigen exposure is detrimental for T cell function. How TMB affects CD4 and CD8 T cell differentiation in untreated tumours, and whether this affects patient outcomes is unknown. Here we paired high-dimensional flow cytometry, exome, single-cell and bulk RNA sequencing from patients with resected, untreated NSCLC to examine these relationships. TMB was associated with compartment-wide T cell differentiation skewing, characterized by loss of TCF7-expressing progenitor-like CD4 T cells, and an increased abundance of dysfunctional CD8 and CD4 T cell subsets, with significant phenotypic and transcriptional similarity to neoantigen-reactive CD8 T cells. A gene signature of redistribution from progenitor-like to dysfunctional states associated with poor survival in lung and other cancer cohorts. Single-cell characterization of these populations informs potential strategies for therapeutic manipulation in NSCLC.
Publisher: Elsevier BV
Date: 10-2014
Publisher: Springer Science and Business Media LLC
Date: 08-01-2015
DOI: 10.1038/NCOMMS6751
Abstract: Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P =3.95 × 10 −15 ) and HLA-B (rs2922994, P =2.43 × 10 −9 ) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility.
Publisher: Springer Science and Business Media LLC
Date: 09-03-2016
DOI: 10.1038/NCOMMS10933
Abstract: Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES , P =2.55 × 10 −11 ), 6p25.2 (rs73718779, SERPINB6 , P =1.97 × 10 −8 ) and 3q28 (rs9815073, LPP , P =3.62 × 10 −8 ), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11 , P =1.00 × 10 −11 ) in the combined analysis. We find suggestive evidence ( P × 10 −7 ) for two additional new loci at 4q24 (rs10028805, BANK1 , P =7.19 × 10 −8 ) and 3p22.2 (rs1274963, CSRNP1 , P =2.12 × 10 −7 ). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.
Publisher: Springer Science and Business Media LLC
Date: 16-06-2013
DOI: 10.1038/NG.2652
Publisher: Springer Science and Business Media LLC
Date: 28-09-2014
DOI: 10.1038/NG.3105
Publisher: Herpetologists League
Date: 12-2018
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Anderson Kennedy Soares De-Lima.