Clinical & Translational Immunology

The Omega-6 Lipid pathway shift is associated with neutrophil influx and structural lung damage in early cystic fibrosis lung disease
Slimmen LJ, Broos JY, Manaï BH, Estevão SC, Giera M, Kooij G, Unger WW and Janssens HM
In cystic fibrosis (CF), an imbalanced lipid metabolism is associated with lung inflammation. Little is known about the role that specific lipid mediators (LMs) exert in CF lung inflammation, and whether their levels change during early disease progression. Therefore, we measured airway LM profiles of young CF patients, correlating these with disease-associated parameters.
Siglec-7 and Siglec-9 expression in primary triple negative and oestrogen receptor positive breast cancer and signalling
van Houtum EJ, Valk AH, Granado D, Lok J, van den Bogaard L, Remkes N, van Eck van der Sluijs J, Span PN, Cornelissen LA and Adema GJ
PD-1/PD-L1 immune checkpoint blockade can be an effective treatment for advanced breast cancer patients. However, patients with oestrogen receptor positive (ER+) tumors often display only low lymphocyte infiltration, while a large part of triple negative (TN) breast tumors does not generate an effective immunotherapy response. Therefore, new treatment strategies have to be developed. Here, we investigate Siglec-7 and Siglec-9 as novel ITIM-bearing inhibitory immune checkpoint receptors similar to PD-1, but expressed on a broader range of immune cells.
Biomarkers to predict and diagnose pulmonary complications in children post haematopoietic stem cell transplant
Walker H, Haeusler GM, Cole T, Neeland M, Hanna D and Shanthikumar S
Haematopoietic cell transplant (HCT) is a cellular therapy for a group of high-risk children with cancer, immunodeficiency and metabolic disorders. Whilst curative for a child's underlying condition, HCT has significant risks associated, including lung injury. These complications are associated with increased post HCT mortality and require improved methods of risk stratification, diagnosis and treatment.
Pulmonary complications post allogeneic haematopoietic stem cell transplant in children
Walker H, Abbotsford J, Haeusler GM, Yeoh D, Ramachandran S, Ng M, Holzmann J, Shanthikumar S, Weerdenburg H, Hanna D, Neeland MR and Cole T
Haematopoietic stem cell transplant (HCT) is a cellular therapy that, whilst curative for a child's underlying disease, carries significant risk of mortality, including because of pulmonary complications. The aims of this study were to describe the burden of pulmonary complications post-HCT in a cohort of Australian children and identify risk factors for the development of these complications.
excretory/secretory products: an untapped library of tolerogenic immunotherapeutics against food allergy
Rogers M, Kamath S, McManus D, Jones M, Gordon C and Navarro S
Food allergy (FA) is considered the 'second wave' of the allergy epidemic in developed countries after asthma and allergic rhinitis with a steadily growing burden of 40%. The absence of early childhood pathogen stimulation embodied by the hygiene hypothesis is one explanation, and in particular, the eradication of parasitic helminths could be at play. Infections with parasites spp. have been found to have a negative correlation with allergic diseases. Schistosomes induce regulatory responses to evade immune detection and ensure their long-term survival. This is achieved via excretory/secretory (E/S) products, consisting of proteins, lipids, metabolites, nucleic acids and extracellular vesicles, representing an untapped therapeutic avenue for the treatment of FA without the unpleasant side-effects and risks associated with live infection. Schistosome-derived immunotherapeutic development is in its infancy and novel discoveries are heavily technology dependent; thus, it is essential to better understand how newly identified molecules interact with host immune systems to ensure safety and successful translation. This review will outline the identified -derived E/S products at all life cycle stages and discuss known mechanisms of action and their ability to suppress FA.
Cord blood granulocyte levels are associated with severe bronchiolitis in the first year of life
Martins Costa Gomes G, Da Silva Sena CR, Murphy VE, Hansbro PM, Starkey MR, Gibson PG, Mattes J and Collison AM
Bronchiolitis is a leading cause of infant hospitalisation in the first year of life, and it preferentially affects infants born to mothers with asthma. Here, we evaluate cord blood granulocytes in infants born to mothers with asthma participating in the Breathing for Life Trial (BLT), to investigate early life determinants of bronchiolitis hospitalisation within the first year of life.
Autologous Epstein-Barr virus-specific adoptive T-cell therapy in a patient with lupus nephritis
Ranganathan D, Leibowitz S, John GT, Neller MA, Ambalathingal GR, Beagley L, Panikkar A, Best S, Raju J, Reddiex H, Ratanjee S, Ng MSY, Smith C and Khanna R
Dysregulation of Epstein-Barr virus (EBV)-specific cellular immunity has been hypothesised as one of the contributing factors in the pathogenesis of systemic lupus erythematosus (SLE). Lupus nephritis is a major risk factor for overall morbidity in SLE. Immune-based strategies directed to EBV have been proposed as potential therapeutic strategy for SLE and lupus nephritis.
Spatial proteomic profiling of tumor and stromal compartments in non-small-cell lung cancer identifies signatures associated with overall survival
Yaghoubi Naei V, Monkman J, Sadeghirad H, Mehdi A, Blick T, Mullally W, O'Byrne K, Warkiani ME and Kulasinghe A
Non-small-cell lung carcinoma (NSCLC) is the most prevalent and lethal form of lung cancer. The need for biomarker-informed stratification of targeted therapies has underpinned the need to uncover the underlying properties of the tumor microenvironment (TME) through high-plex quantitative assays.
Primary SARS-CoV-2 infection in children and adults results in similar Fc-mediated antibody effector function patterns
Gelderloos AT, Lakerveld AJ, Schepp RM, Nicolaie MA, van Beek J, Beckers L, van Binnendijk RS, Rots NY and van Kasteren PB
Increasing evidence suggests that Fc-mediated antibody effector functions have an important role in protection against respiratory viruses, including SARS-CoV-2. However, limited data are available on the potential differences in the development, heterogeneity and durability of these responses in children compared to adults.
Humoral and cellular immune responses in vaccinated and unvaccinated children following SARS-CoV-2 Omicron infection
Toh ZQ, Anderson J, Mazarakis N, Quah L, Nguyen J, Higgins RA, Do LAH, Ng YY, Jalali S, Neeland MR, McMinn A, Saffery R, McNab S, McVernon J, Marcato A, Burgner DP, Curtis N, Steer AC, Mulholland K, Pellicci DG, Crawford NW, Tosif S and Licciardi PV
The immune response in children elicited by SARS-CoV-2 Omicron infection alone or in combination with COVID-19 vaccination (hybrid immunity) is poorly understood. We examined the humoral and cellular immune response following SARS-CoV-2 Omicron infection in unvaccinated children and children who were previously vaccinated with COVID-19 mRNA vaccine.
Lymphocyte activation gene 3 served as a potential prognostic and immunological biomarker across various cancer types: a clinical and pan-cancer analysis
Liu Y, Yao Y, Yang X, Wei M, Lu B, Dong K, Lyu D, Li Y, Guan W, Huang R, Xu G and Pan X
Lymphocyte activation gene 3 (LAG3), an inhibitory receptor in T-cell activation, is a negative prognostic factor. However, its impact on tumours has yet to be comprehensively elucidated on a pan-cancer scale. Thus, we aim to reveal its role at the pan-cancer level.
Naturally acquired adaptive immunity to is impaired in rheumatoid arthritis patients
Ercoli G, Selway-Clarke H, Truijen D, Folkmanaite M, Oulton T, Norris-Grey C, Nakajima R, Felgner P, Wren BW, Tetteh K, Croucher NJ, Leandro M, Cambridge G and Brown JS
Patients with rheumatoid arthritis (RA) have an increased susceptibility to infections, including those caused by . Why RA is associated with increased susceptibility to is poorly understood. This study aims to assess the effects of RA and B-cell depletion therapy on naturally acquired antibody responses to 289  protein antigens using a novel protein array.
IL-15-induced CD38HLA-DRCD8 T cells correlate with liver injury via NKG2D in chronic hepatitis B cirrhosis
Fan J, Xu M, Liu K, Yan W, Wu H, Dong H, Yang Y and Ye W
CD8 T cells play a critical role in the immune dysfunction associated with liver cirrhosis. CD38HLA-DRCD8 T cells, or bystander-activated CD8 T cells, are involved in tissue injury but their specific contribution to liver cirrhosis remains unclear. This study sought to identify the mechanism for CD38HLA-DRCD8 T cell-mediated pathogenesis during liver cirrhosis.
Inhibitory effect of hydroxychloroquine on glucocorticoid-induced osteoporosis in lupus therapy
Qiu W, Han X, Yu T, Jiang L, Wang X, Feng R, Duan X, Teng Y, Yin H, Bokarewa MI and Deng GM
Systemic lupus erythematosus (SLE) is a chronic and severe autoimmune disease characterised by persistent inflammation. Hydroxychloroquine (HCQ) and glucocorticoids (GCs) are the primary agents commonly used in combination as the first-line treatment for SLE. Nevertheless, the specific mechanisms responsible for the effectiveness of this combined therapy with HCQ and GCs have not been fully elucidated. This study aimed to reveal the mechanism behind combined HCQ and GC treatment in lupus.
Natural killer cell antibody-dependent cellular cytotoxicity to is impacted by cellular phenotypes, erythrocyte polymorphisms, parasite diversity and intensity of transmission
Tukwasibwe S, Lewis SN, Taremwa Y, van der Ploeg K, Press KD, Ty M, Namirimu Nankya F, Musinguzi K, Nansubuga E, Bach F, Chamai M, Okitwi M, Tumusiime G, Nakimuli A, Colucci F, Kamya MR, Nankabirwa JI, Arinaitwe E, Greenhouse B, Dorsey G, Rosenthal PJ, Ssewanyana I and Jagannathan P
Natural killer (NK) cells make important contributions to anti-malarial immunity through antibody-dependent cellular cytotoxicity (ADCC), but the role of different components of this pathway in promoting NK cell activation remains unclear.
Anti-signal recognition particle antibodies induce cardiac diastolic dysfunction via oxidative stress injury
Zhang H, Shi Y, Fan Y, Zhu D, Qiu Z, Chi H, Hu Q, Xie L, Sun Y, Liu H, Cheng X, Ye J, Shi H, Zhou Z, Meng J, Teng J, Yang C, Jin W and Su Y
Anti-signal recognition particle (SRP) antibodies, markers of immune-mediated necrotising myopathy, are reportedly related to cardiac involvement; however, whether they are pathogenic to the myocardium remains unclear. We aimed, therefore, to explore the pathogenicity of anti-SRP antibodies against the myocardium through and studies.
Targeting CD38 with monoclonal antibodies disrupts key survival pathways in paediatric Burkitt's lymphoma malignant B cells
Kläsener K, Herrmann N, Håversen L, Sundell T, Sundqvist M, Lundqvist C, Manna PT, Jonsson CA, Visentini M, Ljung Sass D, McGrath S, Grimstad K, Aranburu A, Mellgren K, Fogelstrand L, Forsman H, Ekwall O, Borén J, Gjertsson I, Reth M, Mårtensson IL and Camponeschi A
Paediatric Burkitt's lymphoma (pBL) is the most common childhood non-Hodgkin B-cell lymphoma. Despite the encouraging survival rates for most children, treating cases with relapse/resistance to current therapies remains challenging. CD38 is a transmembrane protein highly expressed in pBL. This study investigates the effectiveness of CD38-targeting monoclonal antibodies (mAbs), daratumumab and isatuximab, in impairing crucial cellular processes and survival pathways in pBL malignant cells.
Serological responses and clinical outcomes following a three-dose primary COVID-19 vaccine schedule in kidney transplant recipients and people on dialysis
Tharmaraj D, Boo I, O'Hara J, Sun S, Polkinghorne KR, Dendle C, Turner SJ, van Zelm MC, Drummer HE, Khoury G and Mulley WR
Despite vaccination strategies, people with chronic kidney disease, particularly kidney transplant recipients (KTRs), remained at high risk of poor COVID-19 outcomes. We assessed serological responses to the three-dose COVID-19 vaccine schedule in KTRs and people on dialysis, as well as seroresponse predictors and the relationship between responses and breakthrough infection.
Characteristics of PD-1CD4 T cells in peripheral blood and synovium of rheumatoid arthritis patients
Chen YJ, Chen Y, Chen P, Jia YQ, Wang H and Hong XP
PD-1 plays a crucial role in the immune dysregulation of rheumatoid arthritis (RA), but the specific characteristics of PD-1CD4 T cells remain unclear and require further investigation.
Endogenous bystander killing mechanisms enhance the activity of novel FAP-specific CAR-T cells against glioblastoma
Yu W, Truong NT, Polara R, Gargett T, Tea MN, Pitson SM, Cockshell MP, Bonder CS, Ebert LM and Brown MP
CAR-T cells are being investigated as a novel immunotherapy for glioblastoma, but clinical success has been limited. We recently described fibroblast activation protein (FAP) as an ideal target antigen for glioblastoma immunotherapy, with expression on both tumor cells and tumor blood vessels. However, CAR-T cells targeting FAP have never been investigated as a therapy for glioblastoma.
The contribution of the CRP/CD64 axis to renal cancer progression by inducing protumor activation of tumor-associated macrophages
Pan C, Fujiwara Y, Yano H, Anami T, Ibe Y, Li L, Miura Y, Motoshima T, Esumi S, Yatsuda J, Hibi T, Kamba T and Komohara Y
C-reactive protein (CRP) is a well-known acute-phase protein that increases remarkably under various inflammatory conditions and is elevated in patients with malignant tumors. In this study, we investigated the influence of CRP on the tumor microenvironment in clear cell renal cell carcinoma (ccRCC).