Placental Galectins Are Key Players in Regulating the Maternal Adaptive Immune Response

Balogh, Andrea; Tóth, Eszter; Romero, Roberto; Paréj, Katalin; Csala, Diana; Szenasi, Nikolett L.; Hajdú, István; Juhász, Kata; Kovács, Árpád Ferenc; Meiri, Hamutal; Hupuczi, Petronella; Tarca, Adi L.; Hassan, Sonia S.; Erez, Offer; Závodszky, Péter; Matkó, János; Papp, Zoltán; Rossi, Simona W.; Hahn, Sinuhe; Pállinger, Éva; Than, Nándor Gábor

doi:10.3389/fimmu.2019.01240

Cited by 57 publications

(80 citation statements)

References 198 publications

(146 reference statements)

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“…ANXA5, which also displayed a CNA loss, encodes the protein Annexin V, which is involved in stabilization of the T cell receptor (TCR) and peptide-MHC interactions during formation of an immunological synapse [25]. Galectin-14 (LGALS14) is expressed mainly by the placenta and was shown to be able to induce apoptosis of activated T lymphocytes [4]. The gene FGL1 encodes for a protein called fibrinogenlike protein 1, which was recently described to be highly expressed in many cancers and to inhibit antigenspecific T cell activation through the interaction with the known checkpoint molecule Lag-3 [47].…”

Section: Resultsmentioning

confidence: 99%

Molecular profiling of an osseous metastasis in glioblastoma during checkpoint inhibition: potential mechanisms of immune escape

Mohme

Maire

Schliffke

et al. 2020

acta neuropathol commun

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Peripheral metastases of glioblastoma (GBM) are very rare despite the ability of GBM cells to pass through the blood-brain barrier and be disseminated through the peripheral blood. Here, we describe a detailed genetic and immunological characterization of a GBM metastasis in the skeleton, which occurred during anti-PD-1 immune checkpoint therapy. We performed whole genome sequencing (WGS) and 850 K methylation profiling of the primary and recurrent intracranial GBM as well as one of the bone metastases. Copy number alterations (CNA) and mutational profiles were compared to known genomic alterations in the TCGA data base. In addition, immunophenotyping of the peripheral blood was performed. The patient who was primarily diagnosed with IDHwildtype GBM. After the resection of the first recurrence, progressive intracranial re-growth was again detected, and chemotherapy was replaced by PD-1 checkpoint inhibition, which led to a complete intracranial remission. Two months later MR-imaging revealed multiple osseous lesions. Biopsy confirmed the GBM origin of the skeleton metastases. Immunophenotyping reflected the effective activation of a peripheral T-cell response, with, however, increase of regulatory T cells during disease progression. WGS sequencing demonstrated distinct genomic alterations of the GBM metastasis, with gains along chromosomes 3 and 9 and losses along chromosome 4, 10, and 11. Mutational analysis showed mutations in potentially immunologically relevant regions. Additionally, we correlated tumour-infiltrating lymphocyte and microglia presence to the occurrence of circulating tumour cells (CTCs) in a larger cohort and found a decreased infiltration of cytotoxic T cells in patients positive for CTCs. This study exemplifies that the tumour microenvironment may dictate the response to immune checkpoint therapy. In addition, our study highlights the fact that despite an effective control of intracranial GBM, certain tumour clones have the ability to evade the tumour-specific T-cell response and cause progression even outside of the CNS.

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Section: Resultsmentioning

confidence: 99%

Molecular profiling of an osseous metastasis in glioblastoma during checkpoint inhibition: potential mechanisms of immune escape

Mohme

Maire

Schliffke

et al. 2020

acta neuropathol commun

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“…A comprehensive set of studies on placental galectins was performed by Than and co-authors that revealed crucial properties and functions of these genes and proteins in trophoblast differentiation and placenta development [ 4 , 196 , 197 ]. First, human genes encoding these galectins ( LGALS13 , LGALS14 , and LGALS16 ) are localized in a specific cluster on chromosome 19, which is evolutionary conserved in primates.…”

Section: Galectins-13 -14 and -16mentioning

confidence: 99%

The Emerging Role of Galectins and O-GlcNAc Homeostasis in Processes of Cellular Differentiation

Tazhitdinova

Timoshenko

2020

Cells

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Galectins are a family of soluble β-galactoside-binding proteins with diverse glycan-dependent and glycan-independent functions outside and inside the cell. Human cells express twelve out of sixteen recognized mammalian galectin genes and their expression profiles are very different between cell types and tissues. In this review, we summarize the current knowledge on the changes in the expression of individual galectins at mRNA and protein levels in different types of differentiating cells and the effects of recombinant galectins on cellular differentiation. A new model of galectin regulation is proposed considering the change in O-GlcNAc homeostasis between progenitor/stem cells and mature differentiated cells. The recognition of galectins as regulatory factors controlling cell differentiation and self-renewal is essential for developmental and cancer biology to develop innovative strategies for prevention and targeted treatment of proliferative diseases, tissue regeneration, and stem-cell therapy.

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“…Several identified genes also exhibited signatures of natural selection. One example region putatively under balancing selection includes two deletions impacting the primate-expanded galectin gene cluster, a family of proteins that specifically bind β-galactoside sugars and are important in modulating immune response through interactions with T cells [86]. Both deletions (10 kbp and 35 kbp in size, respectively) are found homozygously in all chimpanzees tested (n = 25), and thus are likely not the target of balancing selection, but they completely ablated CLC (or LGALS10) and LGALS14, as well as the downstream region of LGALS13 ( Figure S9).…”

Section: Discussionmentioning

confidence: 99%

Identification of Structural Variation in Chimpanzees Using Optical Mapping and Nanopore Sequencing

Soto

Shew

Mastoras

et al. 2020

Genes

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Recent efforts to comprehensively characterize great ape genetic diversity using short-read sequencing and single-nucleotide variants have led to important discoveries related to selection within species, demographic history, and lineage-specific traits. Structural variants (SVs), including deletions and inversions, comprise a larger proportion of genetic differences between and within species, making them an important yet understudied source of trait divergence. Here, we used a combination of long-read and -range sequencing approaches to characterize the structural variant landscape of two additional Pan troglodytes verus individuals, one of whom carries 13% admixture from Pan troglodytes troglodytes. We performed optical mapping of both individuals followed by nanopore sequencing of one individual. Filtering for larger variants (>10 kbp) and combined with genotyping of SVs using short-read data from the Great Ape Genome Project, we identified 425 deletions and 59 inversions, of which 88 and 36, respectively, were novel. Compared with gene expression in humans, we found a significant enrichment of chimpanzee genes with differential expression in lymphoblastoid cell lines and induced pluripotent stem cells, both within deletions and near inversion breakpoints. We examined chromatin-conformation maps from human and chimpanzee using these same cell types and observed alterations in genomic interactions at SV breakpoints. Finally, we focused on 56 genes impacted by SVs in >90% of chimpanzees and absent in humans and gorillas, which may contribute to chimpanzee-specific features. Sequencing a greater set of individuals from diverse subspecies will be critical to establish the complete landscape of genetic variation in chimpanzees.

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Placental Galectins Are Key Players in Regulating the Maternal Adaptive Immune Response

Cited by 57 publications

References 198 publications

Molecular profiling of an osseous metastasis in glioblastoma during checkpoint inhibition: potential mechanisms of immune escape

Molecular profiling of an osseous metastasis in glioblastoma during checkpoint inhibition: potential mechanisms of immune escape

The Emerging Role of Galectins and O-GlcNAc Homeostasis in Processes of Cellular Differentiation

Identification of Structural Variation in Chimpanzees Using Optical Mapping and Nanopore Sequencing

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