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Pharmacogenomic and epigenomic approaches to untangle the enigma of IL-10 blockade in oncology.

ABSTRACT: The host immune system status remains an unresolved mystery among several malignancies. An immune-compromised state or smart immune-surveillance tactics orchestrated by cancer cells are the primary cause of cancer invasion and metastasis. Taking a closer look at the tumour-immune microenvironment, a complex network and crosstalk between infiltrating immune cells and cancer cells mediated by cytokines, chemokines, exosomal mediators and shed ligands are present. Cytokines such as interleukins can influence all components of the tumour microenvironment (TME), consequently promoting or suppressing tumour invasion based on their secreting source. Interleukin-10 (IL-10) is an interlocked cytokine that has been associated with several types of malignancies and proved to have paradoxical effects. IL-10 has multiple functions on cellular and non-cellular components within the TME. In this review, the authors shed the light on the regulatory role of IL-10 in the TME of several malignant contexts. Moreover, detailed epigenomic and pharmacogenomic approaches for the regulation of IL-10 were presented and discussed.

SUBMITTER: Elemam NM

PROVIDER: S-EPMC10941350 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Pharmacogenomic and epigenomic approaches to untangle the enigma of IL-10 blockade in oncology.

Elemam Noha M NM Mekky Radwa Y RY Rashid Gowhar G Braoudaki Maria M Youness Rana A RA

Expert reviews in molecular medicine 20240108

The host immune system status remains an unresolved mystery among several malignancies. An immune-compromised state or smart immune-surveillance tactics orchestrated by cancer cells are the primary cause of cancer invasion and metastasis. Taking a closer look at the tumour-immune microenvironment, a complex network and crosstalk between infiltrating immune cells and cancer cells mediated by cytokines, chemokines, exosomal mediators and shed ligands are present. Cytokines such as interleukins can ...[more]

PMID: 38186186

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Project description:BackgroundDeep-branching phylogenetic relationships are often difficult to resolve because phylogenetic signals are obscured by the long history and complexity of evolutionary processes, such as ancient introgression/hybridization, polyploidization, and incomplete lineage sorting (ILS). Phylogenomics has been effective in providing information for resolving both deep- and shallow-scale relationships across all branches of the tree of life. The olive family (Oleaceae) is composed of 25 genera classified into five tribes with tribe Oleeae consisting of four subtribes. Previous phylogenetic analyses showed that ILS and/or hybridization led to phylogenetic incongruence in the family. It was essential to distinguish phylogenetic signal conflicts, and explore mechanisms for the uncertainties concerning relationships of the olive family, especially at the deep-branching nodes.ResultsWe used the whole plastid genome and nuclear single nucleotide polymorphism (SNP) data to infer the phylogenetic relationships and to assess the variation and rates among the main clades of the olive family. We also used 2608 and 1865 orthologous nuclear genes to infer the deep-branching relationships among tribes of Oleaceae and subtribes of tribe Oleeae, respectively. Concatenated and coalescence trees based on the plastid genome, nuclear SNPs and multiple nuclear genes suggest events of ILS and/or ancient introgression during the diversification of Oleaceae. Additionally, there was extreme heterogeneity in the substitution rates across the tribes. Furthermore, our results supported that introgression/hybridization, rather than ILS, is the main factor for phylogenetic discordance among the five tribes of Oleaceae. The tribe Oleeae is supported to have originated via ancient hybridization and polyploidy, and its most likely parentages are the ancestral lineage of Jasmineae or its sister group, which is a "ghost lineage," and Forsythieae. However, ILS and ancient introgression are mainly responsible for the phylogenetic discordance among the four subtribes of tribe Oleeae.ConclusionsThis study showcases that using multiple sequence datasets (plastid genomes, nuclear SNPs and thousands of nuclear genes) and diverse phylogenomic methods such as data partition, heterogeneous models, quantifying introgression via branch lengths (QuIBL) analysis, and species network analysis can facilitate untangling long and complex evolutionary processes of ancient introgression, paleopolyploidization, and ILS.

Project description:BackgroundGermline and tumor pharmacogenomics impact drug responses, but germline markers less commonly guide oncology prescribing. The authors hypothesized that a critical number of clinically actionable germline pharmacogenomic associations exist, representing clinical implementation opportunities.MethodsIn total, 125 oncology drugs were analyzed for positive germline pharmacogenomic associations in journals with impact factors ≥5. Studies were assessed for design and genotyping quality, clinically relevant outcomes, statistical rigor, and evidence of drug-gene effects. Associations from studies of high methodologic quality were deemed potentially clinically actionable, and translational summaries were written as point-of-care clinical decision support (CDS) tools and formally evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument.ResultsThe authors identified germline pharmacogenomic results for 56 of 125 oncology drugs (45%) across 173 publications. Actionable associations were detected for 12 drugs, including 6 that had germline pharmacogenomic information within US Food and Drug Administration labels or published guidelines (capecitabine/fluorouracil/dihydropyrimidine dehydrogenase [DPYD], irinotecan/uridine diphosphate glucuronosyltransferase family 1 member A1 [UGT1A1], mercaptopurine/thioguanine/thiopurine S-methyltransferase [TPMT], tamoxifen/cytochrome P450 [CYP] family 2 subfamily D member 6 [CYP2D6]), and 6 others were novel (asparaginase/nuclear factor of activated T-cells 2 [NFATC2]/human leukocyte antigen D-related β1 [HLA-DRB1], cisplatin/acylphosphatase 2 [ACYP2], doxorubicin/adenosine triphosphate-binding cassette subfamily C member 2/Rac family small guanosine triphosphatase 2/neutrophil cytosolic factor 4 [ABCC2/RAC2/NCF4], lapatinib/human leukocyte antigen DQ α1 [HLA-DQA1], sunitinib/cytochrome P450 family 3 subfamily A member 5 [CYP3A5], vincristine/centrosomal protein 72 [CEP72]). By using AGREE II, the developed CDS summaries had high mean ± standard deviation scores (maximum score, 100) for scope and purpose (92.7 ± 5.1) and rigour of development (87.6 ± 7.4) and moderate yet robust scores for clarity of presentation (58.6 ± 25.1) and applicability (55.9 ± 24.6). The overall mean guideline quality score was 5.2 ± 1.0 (maximum score, 7). Germline pharmacogenomic CDS summaries for these 12 drugs were recommended for implementation.ConclusionsSeveral oncology drugs have actionable germline pharmacogenomic information, justifying their delivery through institutional pharmacogenomic implementations to determine clinical utility. Cancer 2018;124:3052-65. © 2018 American Cancer Society.

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Pharmacogenomic and epigenomic approaches to untangle the enigma of IL-10 blockade in oncology.

Publications

Pharmacogenomic and epigenomic approaches to untangle the enigma of IL-10 blockade in oncology.

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