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Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion
SARS-CoV-2 evolved into several sublineages harboring different mutations in spike. Here, the authors isolate and characterize nine SARS-CoV-2 variants and show that EG.5.1.3 has highest fitness in nasal epithelial cells, while JN.1 shows lower affinity to ACE2 and higher immune evasion compared to BA.2.86.1.
- Delphine Planas
- , Isabelle Staropoli
- & Olivier Schwartz
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Article
| Open Access
Altered receptor binding, antibody evasion and retention of T cell recognition by the SARS-CoV-2 XBB.1.5 spike protein
New variants of SARS-CoV-2 virus can evolve such that antibodies that recognised previous versions are not able to recognise newer versions. Here the authors characterise antibody binding to the XBB.1.5 variant and how antibodies and T cells from persons infected with earlier versions of SARS-CoV-2 are able to recognise and/or bind to the XBB.1.5 spike protein.
- Dhiraj Mannar
- , James W. Saville
- & Sriram Subramaniam
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Converging and evolving immuno-genomic routes toward immune escape in breast cancer
Immune response during breast cancer progression remains to be explored. Here, the characterisation of sequential and parallel multiregion samples of an index patient and a cohort of metastatic triple-negative breast cancers reveals convergent immune evasion mechanisms and an increase in tumor genomic heterogeneity.
- Juan Blanco-Heredia
- , Carla Anjos Souza
- & Leticia De Mattos-Arruda
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PAF1c links S-phase progression to immune evasion and MYC function in pancreatic carcinoma
MYC drives S-phase progression and immune invasion in pancreatic ductal adenocarcinoma (PDAC), but the underlying mechanisms are not fully understood. Here, the authors show that the transcription elongation complex PAF1c controls the competition of different gene sets for RNA polymerase and elongation factors to regulate these MYC-associated mechanisms in PDAC.
- Abdallah Gaballa
- , Anneli Gebhardt-Wolf
- & Martin Eilers
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HKDC1 promotes tumor immune evasion in hepatocellular carcinoma by coupling cytoskeleton to STAT1 activation and PD-L1 expression
Aberrant expression of the human hexokinase HKDC1 has been observed in patients with cancer. Here the authors report that HKDC1 expression is associated with hepatocellular carcinoma progression and PD-L1 mediated immune evasion.
- Yi Zhang
- , Mingjie Wang
- & Ping Gao
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Article
| Open Access
A cytomegalovirus inflammasome inhibitor reduces proinflammatory cytokine release and pyroptosis
Viruses have evolved specific mechanisms to reduce programmed cell death in order to prolong survival. Here the authors show a mouse cytomegalovirus (MCMV) encoded protein that inhibits pyroptosis, proinflammatory cytokine release and the assembly of inflammasomes.
- Yingqi Deng
- , Eleonore Ostermann
- & Wolfram Brune
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| Open Access
Single cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets
The use of single cell sequencing has enabled more detailed analysis of the immune response to infection. Here the authors characterise the immune response to malaria infection in an endemic region using single cell transcriptomics indicating regulatory signatures associated with infection.
- Nicholas L. Dooley
- , Tinashe G. Chabikwa
- & Michelle J. Boyle
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Continually recruited naïve T cells contribute to the follicular helper and regulatory T cell pools in germinal centers
B cell clonal expansion and affinity maturation takes place in germinal centers (GC) and is orchestrated by follicular T cells. Here authors show that naïve conventional T cells are continuously recruited to the GCs during the GC reaction and develop into follicular helper and regulatory T cells, thus quantitatively contribute to remodelling the GC overtime.
- Julia Merkenschlager
- , Riza-Maria Berz
- & Michel C. Nussenzweig
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Activation of melanocortin-1 receptor signaling in melanoma cells impairs T cell infiltration to dampen antitumor immunity
Aberrant G protein-coupled receptor (GPCR) signaling has been associated with tumor progression and metastasis. Here the authors show that depletion of the GPCR melanocortin-1 receptor (MC1R) in melanoma cells is associated with enhanced T cell infiltration and anti-tumor immune responses.
- Yazhong Cui
- , Yang Miao
- & Ting Han
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Article
| Open Access
mRNA 3’UTR lengthening by alternative polyadenylation attenuates inflammatory responses and correlates with virulence of Influenza A virus
Here, Bergant et al. provide evidence that Influenza A viruses cause alternative polyadenylation of host mRNAs and abrogation of this function leads to an attenuated phenotype in mice. This may constitute a general immune evasive mechanism employed by a variety of pathogenic viruses.
- Valter Bergant
- , Daniel Schnepf
- & Andreas Pichlmair
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Loss of PHF8 induces a viral mimicry response by activating endogenous retrotransposons
The role of PHD finger protein 8 (PHF8) in anti-tumour immunity remains to be investigated. Here, the authors suggest PHF8 as an epigenetic checkpoint and show that targeting PHF8 induces a viral mimicry response enhancing anti-tumour immunity in colorectal cancer.
- Yanan Liu
- , Longmiao Hu
- & Xiufeng Pang
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Vaccinia E5 is a major inhibitor of the DNA sensor cGAS
The cGAS-STING signalling pathway is critical in mediating host antiviral immunity. Here, Yang et al screen vaccinia viral genes to identify and then characterise that the viral protein E5 is a major inhibitor of cGAS by mediating cGAS ubiquitination and degradation.
- Ning Yang
- , Yi Wang
- & Liang Deng
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| Open Access
A bacterial autotransporter impairs innate immune responses by targeting the transcription factor TFE3
Innate immune evasion is a key aspect of bacterial pathogenesis. Here, Ta et al identify and characterise EhaF, a bacterial autotransporter that functions to inhibit host innate immunity and promote the colonisation and pathogenesis of enterohemorrhagic Escherichia coli.
- Atri Ta
- , Rafael Ricci-Azevedo
- & Sivapriya Kailasan Vanaja
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Total escape of SARS-CoV-2 from dual monoclonal antibody therapy in an immunocompromised patient
Antibodies against SARS-CoV-2 can be used to treat infections but there is a risk of driving viral resistance to antibodies. Here the authors characterise SARS-CoV-2 escape mutants from an immunocompromised patient treated with anti-SARS-CoV-2 antibodies using mouse protection studies and structural prediction.
- Lena Jaki
- , Sebastian Weigang
- & Jonas Fuchs
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| Open Access
Single cell analysis in head and neck cancer reveals potential immune evasion mechanisms during early metastasis
The molecular mechanisms underlying lymph-node metastasis in head and neck squamous-cell carcinoma remain to be investigated. Here, the authors perform single-cell RNA sequencing of cancer cells and CD8 + T cells and suggest potential mechanisms of immune evasion during early metastasis.
- Hong Sheng Quah
- , Elaine Yiqun Cao
- & N. Gopalakrishna Iyer
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A trans-kingdom T6SS effector induces the fragmentation of the mitochondrial network and activates innate immune receptor NLRX1 to promote infection
Bacteria can affect cellular processes in other bacteria and in eukaryotic cells by injecting effectors using a type VI secretion system (T6SS). Here, Sá-Pessoa et al. describe how a T6SS effector from the bacterial pathogen Klebsiella pneumoniae triggers the fragmentation of the mitochondrial network in eukaryotic cells.
- Joana Sá-Pessoa
- , Sara López-Montesino
- & José A. Bengoechea
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Resistance of Omicron subvariants BA.2.75.2, BA.4.6, and BQ.1.1 to neutralizing antibodies
In this work, Planas et al. report that Omicron subvariants BA.2.75.2, BA.4.6, and BQ.1.1 escape neutralization from monoclonal antibodies, and sera from vaccinated individuals with or without Omicron BA.1/2 or BA.5 breakthrough infection.
- Delphine Planas
- , Timothée Bruel
- & Olivier Schwartz
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| Open Access
Epistasis lowers the genetic barrier to SARS-CoV-2 neutralizing antibody escape
Witte et al show that previously acquired substitutions in the SARS-CoV-2 spike protein enable the acquisition of new antibody escape substitutions. New and old substitutions interact to enable escape from broadly neutralizing antibodies.
- Leander Witte
- , Viren A. Baharani
- & Paul D. Bieniasz
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| Open Access
Identification of human progenitors of exhausted CD8+ T cells associated with elevated IFN-γ response in early phase of viral infection
The early immune response following exposure to HCV is not fully explored. Here the authors use single cell analysis and immune profiling to relate the infection sequence and immune response to early HCV infection showing that exhausted phenotypes of T cells arise early post infection.
- Curtis Cai
- , Jerome Samir
- & Fabio Luciani
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| Open Access
Antigenic sin of wild-type SARS-CoV-2 vaccine shapes poor cross-neutralization of BA.4/5/2.75 subvariants in BA.2 breakthrough infections
Updated vaccines based on Omicron subvariants have started to being rolled out. Analysis of antibody response in individuals with two or three vaccine doses suggests that BA.2 breakthrough infection barely increases cross-neutralization capacity against BA.4/5 or BA.2.75.
- Bin Ju
- , Qing Fan
- & Zheng Zhang
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| Open Access
Metabolic control of CD47 expression through LAT2-mediated amino acid uptake promotes tumor immune evasion
Chemo-resistance and immune evasion are major challenges in osteosarcoma treatment. Here the authors show that doxorubicin promotes IL-18 secretion by tumor associated macrophages inducing LAT2-dependent CD47 upregulation in osteosarcoma cells, suggesting LAT2 inhibition as a therapeutic option in combination with doxorubicin.
- Zenan Wang
- , Binghao Li
- & Zhaoming Ye
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| Open Access
The influenza virus PB2 protein evades antiviral innate immunity by inhibiting JAK1/STAT signalling
The PB2 subunit of the RNA polymerase of influenza virus antagonizes interferon signalling. Here, the authors biochemically characterise the molecular interactions that mediate this, and how this impacts viral replication in the context of different influenza subtypes.
- Hui Yang
- , Yurui Dong
- & Xiufan Liu
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Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection
SARS-CoV-2 mutations associated with the escape from antibody-mediated neutralization have been widely reported. Here, in a patient with defective antibody responses, the authors find a potential association between SARS-CoV-2 mutations and CD8 T alterations to implicate possible contributions of CD8 T cells in evasion of SARS-CoV-2 from host immunity.
- Elham Khatamzas
- , Markus H. Antwerpen
- & Andreas Moosmann
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Endowing universal CAR T-cell with immune-evasive properties using TALEN-gene editing
Host versus graft reaction is a major impediment to CAR-T cell immune therapy in allogeneic settings. Authors show here that CAR-T cells, engineered to be deficient in MHC I expression but to express the NK inhibitor HLA-E, are resistant to destruction by both T and NK cells of the host.
- Sumin Jo
- , Shipra Das
- & Julien Valton
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| Open Access
Candida albicans evades NK cell elimination via binding of Agglutinin-Like Sequence proteins to the checkpoint receptor TIGIT
Natural killer cells have emerged as critical immune cells in the response to fungal infection. Here the authors identify how Candida albicans evades the natural killer cell response via expression of ligands that directly modify the natural killer cell response and can be therapeutically targeted to restore the anti-Candida immunity.
- Yoav Charpak-Amikam
- , Tom Lapidus
- & Ofer Mandelboim
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| Open Access
A machine learning algorithm with subclonal sensitivity reveals widespread pan-cancer human leukocyte antigen loss of heterozygosity
Human leukocyte antigen loss of heterozygosity (HLA LOH) is an important mechanism of immune escape in patients with cancer. Here the authors design and validate a machine learning algorithm with subclonal sensitivity for the identification of HLA LOH from paired tumor-normal sequencing data.
- Rachel Marty Pyke
- , Dattatreya Mellacheruvu
- & Sean Michael Boyle
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| Open Access
Loss of Rnf31 and Vps4b sensitizes pancreatic cancer to T cell-mediated killing
Pancreatic cancer is characterized by an immunosuppressive microenvironment, leading to immune evasion. Here, based on in vitro and in vivo CRISPR screens, the authors identify Rnf31 and Vps4b as drivers of immune escape, showing that loss of their function leads to an increase in T cell-mediated killing and reduced tumor growth in preclinical pancreatic cancer models.
- Nina Frey
- , Luigi Tortola
- & Gerald Schwank
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| Open Access
Antibody escape and global spread of SARS-CoV-2 lineage A.27
The A.27 SARS-CoV-2 lineage spread globally in 2021 but did not become dominant. Here, the authors show that A.27 shares some mutations in the spike gene that are present in variants of concern, but lacks the D614G mutation, indicating independent evolution of immune escape properties.
- Tamara Kaleta
- , Lisa Kern
- & Jonas Fuchs
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Maternal-fetal immune responses in pregnant women infected with SARS-CoV-2
As pregnant women are considered vulnerable to SARSCoV-2 infection, it is important to investigate the actual risks involved. The authors show here that, while a T cell-dominant inflammatory response is observed at the maternal-foetal interface, the virus remains undetectable in the placenta but triggers specific immune responses in the neonatal (umbilical cord blood) circulation.
- Valeria Garcia-Flores
- , Roberto Romero
- & Nardhy Gomez-Lopez
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| Open Access
A GATA4-regulated secretory program suppresses tumors through recruitment of cytotoxic CD8 T cells
GATA-binding protein 4 (GATA4) is reported to control cell proliferation in cancers. Here the authors show that GATA4’s pro-inflammatory secretome promotes the recruitment of immune cells such as CD8 + T cells to suppress tumour initiation and growth in a non-cell autonomous manner.
- Rupesh S. Patel
- , Rodrigo Romero
- & Stephen J. Elledge
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Listeria exploits IFITM3 to suppress antibacterial activity in phagocytes
Interferon (IFN) is an important component of antiviral immunity, but can also be exploited by bacteria for immune evasion. Here the authors show that Listeria monocytogenes (Lm) induces type I IFN to suppress the degradation of Lm virulence proteins, ActA and LLO, and promote Lm infection in an IFITM3-dependent manner, thereby hinting at a potential target for antimicrobial therapy.
- Joel M. J. Tan
- , Monica E. Garner
- & John H. Brumell
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| Open Access
TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation
Mycobacterial cell wall lipids can drive immunoevasion, but underlying mechanisms are incompletely understood. Here the authors show TREM2 is a pattern recognition receptor that binds non-glycosylated mycolic acid-containing lipids and inhibits Mincle-induced anti-mycobacterial macrophage responses.
- Ei’ichi Iizasa
- , Yasushi Chuma
- & Hiromitsu Hara
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A slowly cleaved viral signal peptide acts as a protein-integral immune evasion domain
Glycoprotein US9 of human cytomegalovirus downregulates the activating immune ligand MICA*008 to avoid NK cell activation. Here, Seidel et al. show that the signal peptide of US9 is cleaved unusually slowly, causing MICA*008 to be retained in the endoplasmic reticulum (ER) and degraded via the ER quality control system.
- Einat Seidel
- , Liat Dassa
- & Ofer Mandelboim
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| Open Access
Immune suppressive activity of myeloid-derived suppressor cells in cancer requires inactivation of the type I interferon pathway
The role of type I interferon signalling in the control of myeloid derived suppressor cells (MDSC) activity remains controversial. Here the authors show that downregulation of type I interferon receptor is observed in MDSC from cancer patients and tumor-bearing mice and is required for the activation of their immune suppressive properties.
- Kevin Alicea-Torres
- , Emilio Sanseviero
- & Dmitry I. Gabrilovich
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| Open Access
Network models of primary melanoma microenvironments identify key melanoma regulators underlying prognosis
While the molecular profiling of melanoma progression has been extensively characterised by large-scale studies, there is still need for the comprehensive integration of such datasets. Here the authors construct predictive gene network models for prognostic and therapeutic purposes.
- Won-Min Song
- , Praveen Agrawal
- & Bin Zhang
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Article
| Open Access
Common clonal origin of conventional T cells and induced regulatory T cells in breast cancer patients
The mechanisms that shape the regulatory T cell repertoire in patients with cancer are not completely understood. Here, the authors observe that, in breast cancer patients, tumor-resident regulatory T cells do not show clonal relationship with their circulating counterpart, but share a common origin with intratumoral antigen-experienced conventional T cells.
- Maria Xydia
- , Raheleh Rahbari
- & Philipp Beckhove
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Article
| Open Access
β-arrestin 2 as an activator of cGAS-STING signaling and target of viral immune evasion
Excessive interferon (IFN) responses often follow viral infection to induce pathology or even death. Here the authors show that a signaling adaptor, β-arrestin 2, enhances the cGAS/STING innate immunity signaling pathway to promote IFN-β production, but may be degraded in infected cells to serve as a target of viral immune evasion.
- Yihua Zhang
- , Manman Li
- & Dapeng Yan
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Article
| Open Access
Mycobacterium tuberculosis associated with severe tuberculosis evades cytosolic surveillance systems and modulates IL-1β production
Some strains of Mycobacterium tuberculosis seem to be able to avoid host defense systems. Here the authors stratify patients by severity of tuberculosis and find correlations with the level of IL-1β production by macrophages exposed to these isolates.
- Jeremy Sousa
- , Baltazar Cá
- & Margarida Saraiva
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Article
| Open Access
An independent poor-prognosis subtype of breast cancer defined by a distinct tumor immune microenvironment
In breast cancer, the immune infiltration of the tumour associates with clinical outcome. Here, the authors infer immune context based on gene expression data and identify a new independent subtype linked to pro-tumorigenic immune infiltration.
- Xavier Tekpli
- , Tonje Lien
- & Vessela N. Kristensen
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Article
| Open Access
IL-36 promotes anti-viral immunity by boosting sensitivity to IFN-α/β in IRF1 dependent and independent manners
Herpes simplex virus-1 (HSV-1) suppresses the induction of interferon to evade antiviral immunity. Here, Wang et al. show that during HSV-1 infection, IL-36 increases cellular sensitivity to interferon through induction of IRF1 and the interferon receptor.
- Peng Wang
- , Ana M. Gamero
- & Liselotte E. Jensen
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Article
| Open Access
MHC matching fails to prevent long-term rejection of iPSC-derived neurons in non-human primates
Matching iPSC donors’ and patients’ HLA haplotypes has been proposed as a way to generate cell therapy products with enhanced immunological compatibility. Here the authors show that MHC matching alone is insufficient to grant long-term survival of neuronal grafts in the lesioned brain of non-human primates.
- Romina Aron Badin
- , Aurore Bugi
- & Anselme L. Perrier
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Article
| Open Access
Human cytomegalovirus evades antibody-mediated immunity through endoplasmic reticulum-associated degradation of the FcRn receptor
Human cytomegalovirus (HCMV) can persist for the life of a host in the face of robust immune responses owing to a wide range of immune evasion strategies. Here Liu and colleagues show that HCMV evades the IgG-mediated response by the endoplasmic reticulum-associated degradation of the neonatal Fc receptor for IgG.
- Xiaoyang Liu
- , Senthilkumar Palaniyandi
- & Xiaoping Zhu
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| Open Access
Multifunctional CRISPR-Cas9 with engineered immunosilenced human T cell epitopes
Possible immunogenicity of the Cas9 protein raises concerns about therapeutic applications. Here the authors identify pre-existing CD8+T-cell immunity in healthy individuals and in response modify Cas9 to remove the immunodominant epitopes.
- Shayesteh R. Ferdosi
- , Radwa Ewaisha
- & Karen S. Anderson
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| Open Access
Corticosteroids inhibit Mycobacterium tuberculosis-induced necrotic host cell death by abrogating mitochondrial membrane permeability transition
Corticosteroids are host-directed drugs that enhance survival of tuberculosis patients through unclear mechanisms. Here, Gräb et al. show that corticosteroids inhibit necrotic death of cells infected with Mycobacterium tuberculosis by facilitating MKP-1-dependent dephosphorylation of p38 MAPK.
- Jessica Gräb
- , Isabelle Suárez
- & Jan Rybniker
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Article
| Open Access
CD73 expression on effector T cells sustained by TGF-β facilitates tumor resistance to anti-4-1BB/CD137 therapy
Targeting the immune-stimulatory receptor 4-1BB has only yielded modest benefit in cancer treatment. In this study, the authors show that CD73 expression on effector T cells sustained by TGF-β drives tumor resistance to anti-4-1BB therapy and therefore TGF- β blockade can be used to overcome such resistance.
- Siqi Chen
- , Jie Fan
- & Bin Zhang
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Article
| Open Access
A virus-encoded type I interferon decoy receptor enables evasion of host immunity through cell-surface binding
Secreted cytokine decoy receptors encoded by viruses can act as potent immune evasion proteins modulating antiviral immunity. Here Hernaez et al. show that cell surface binding is required for efficient evasion of the host response by a secreted virus encoded type I IFN decoy receptor of vaccinia and ectromelia virus using an in vivo model of infection.
- Bruno Hernáez
- , Juan Manuel Alonso-Lobo
- & Antonio Alcamí
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| Open Access
Chemokines cooperate with TNF to provide protective anti-viral immunity and to enhance inflammation
Cytokines play critical roles in the anti-viral response but their contribution in vivo remains unclear. Here the authors show that viral CrmD is a major virulence determinant and requires the SECRET and TNF binding domains to counter both the chemokine and cytokine driven inflammatory defenses.
- Alí Alejo
- , M. Begoña Ruiz-Argüello
- & Antonio Alcamí
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| Open Access
Oncofetal gene SALL4 reactivation by hepatitis B virus counteracts miR-200c in PD-L1-induced T cell exhaustion
Blocking PD-1 function on T cells is thought to be a viable strategy to prevent virus-induced or tumor-induced T cell exhaustion. Here the authors link the zinc-finger transcription factor SALL4 with miR-200c inhibition of PD-L1 expression by hepatocytes in patients with HBV-induced hepatocellular carcinoma.
- Cheng Sun
- , Peixiang Lan
- & Zhigang Tian
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Article
| Open Access
Human cytomegalovirus-encoded US9 targets MAVS and STING signaling to evade type I interferon immune responses
MAVS and STING signaling are central to interferon-inducing antiviral immunity. Here, the authors show how the human cytomegalovirus protein US9 can evade this immunity by antagonizing these pathways.
- Hyun jin Choi
- , Areum Park
- & Boyoun Park
Semaphorin 3A causes immune suppression by inducing cytoskeletal paralysis in tumour-specific CD8+ T cells