Impact of rosuvastatin on the memory potential and functionality of CD8 T cells from people with HIV.

Background: Virus-specific CD8 T cells play a major role in the natural control of HIV infection, linked to memory-like features such as high survival capacity and polyfunctionality. However, virus-specific CD8 T cells from HIV non-controllers exhibit an effector-like and exhausted profile, with limited antiviral potential. Metabolic reprogramming of cells from non-controllers could reinvigorate their functional capacities.

Donor HLA-DQ genetic and functional divergence affect the control of BK polyoma virus infection after kidney transplantation.

BK polyomavirus (BKPyV) infection remains a major concern after kidney transplantation, increasing the risk of graft loss in the absence of specific antiviral agent now available. Here, we investigated the impact of HLA diversity on the control of posttransplant BKPyV replication. High HLA evolutionary divergence (HED) at the DQ locus in the donor was an independent predictor of BKPyV-free outcome.

Mass cytometry: exploring the immune landscape of systemic autoimmune and inflammatory diseases in the past fourteen years.

Auto-immune and inflammatory diseases are heterogenous in their clinical manifestations and prognosis, even among individuals presenting with the same pathology. Understanding the immunological alterations involved in their pathogenesis provides valuable insights in different clinical phenotypes and treatment responses. Immunophenotyping could lead to significant improvements in diagnosis, monitoring, initial treatment decisions and follow-up in autoimmune and inflammatory diseases.

Role of mucosal-associated invariant T cells dynamics in pathogenesis of Sjögren syndrome.

Sjögren syndrome (SS) is an autoimmune disease characterized by chronic inflammatory infiltrates in the salivary and lacrimal glands. Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T-cells, predominantly found in mucosal tissues with crucial role in epithelial homeostasis. Thus, MAIT cells may be implicated in mucosal alterations of SS patients.

Intravesical Ty21a treatment of non-muscle invasive bladder cancer induces immune responses that correlate with safety and may be associated to therapy potential.

Background: Standard of care treatment of non-muscle invasive bladder cancer (NMIBC) with intravesical Bacillus Calmette Guérin (BCG) is associated with side effects, disease recurrence/progression and supply shortages. We recently showed in a phase I trial (NCT03421236) that intravesical instillation in patients with NMIBC with the maximal tolerated dose of Ty21a/Vivotif, the oral vaccine against typhoid fever, might have a better safety profile. In the present report, we assessed the immunogenicity of intravesical Ty21a in patients of the clinical trial that had received the maximal tolerated dose and compared it with data obtained in patients that had received standard BCG.

Vδ2 T cells are associated with favorable clinical outcomes in patients with bladder cancer and their tumor reactivity can be boosted by BCG and zoledronate treatments.

Bladder cancer is an important public health concern due to its prevalence, high risk of recurrence and associated cost of management. Although BCG instillation for urothelial cancer treatment is the gold-standard treatment for this indication, repeated BCG treatments are associated with significant toxicity and failure, underlining the necessity for alternative or complementary immunotherapy and overall for better understanding of T-cell responses generated within bladder mucosa. Tumor-infiltrating lymphocytes (TIL) have long been recognized as a crucial component of the tumor microenvironment for the control of tumor.

Immune landscape after allo-HSCT: TIGIT- and CD161-expressing CD4 T cells are associated with subsequent leukemia relapse.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective treatment for selected patients with acute myeloid leukemia (AML) and relies on a "graft-versus-leukemia" effect (GVL) where donor T lymphocytes mediate control of malignant cell growth. However, relapse remains the major cause of death after allo-HSCT. In various malignancies, several immunoregulatory mechanisms have been shown to restrain antitumor immunity, including ligand-mediated engagement of inhibitory receptors (IRs) on effector cells, and induction of immunosuppressive cell subsets, such as regulatory T cells (Tregs) or myeloid-derived suppressor cells (MDSCs).

Siglec-7 May Limit Natural Killer Cell-mediated Antitumor responses in Bladder Cancer Patients.

Unlabelled: Aberrant glycosylation actively contributes to tumor progression and is a key hallmark of cancer. Most of the glycan moieties expressed on the surface of cancer cells are sialic acids that may modulate antitumor immune responses binding to sialic acid-binding immunoglobulin-like lectins (Siglecs) expressed by immune cells. Here we show that Siglecs may decrease the bladder tumor immune response mediated by natural killer (NK) cells.

Human MAIT cells are devoid of alloreactive potential: prompting their use as universal cells for adoptive immune therapy.

Background: Mucosal-associated invariant T (MAIT) cells are semi-invariant T cells that recognize microbial antigens presented by the highly conserved MR1 molecule. MAIT cells are predominantly localized in the liver and barrier tissues and are potent effectors of antimicrobial defense. MAIT cells are very few at birth and accumulate gradually over a period of about 6 years during the infancy.

Siglec-6 as a New Potential Immune Checkpoint for Bladder Cancer Patients.

Among the growing family of inhibitory receptors regulating immunity, sialic acid-binding immunoglobulin domain-containing lectins (Siglecs) have recently emerged as immunoregulatory receptors recognizing sialylated ligands on tumor cell surface. However, their role in the immunoregulation of bladder cancer (BCa) remains unknown. Here, we determined the presence of eight Siglec ligands (SLs) on bladder nontumor and tumor cell lines.

Association of Plasma Soluble Vascular Cell Adhesion Molecule-1 and sCD14 With Mortality in HIV-1-Infected West African Adults With High CD4 Counts.

Background: Several biomarkers of inflammation and coagulation were reported to be associated with HIV disease progression in different settings. In this article, we report the association between 11 biomarkers and medium-term mortality in HIV-infected West African adults.

Methods: In Temprano ANRS 12136, antiretroviral therapy (ART)-naive HIV-infected adults with high CD4 counts were randomly assigned either to start ART immediately or defer ART until the World Health Organization criteria were met.

The multifaceted immune regulation of bladder cancer.

Bladder cancer is an important public health concern owing to its prevalence, high recurrence risk and treatment failures. Maintaining the equilibrium between prompt and effective immunity and an excessive and protracted immune response is critical for successful immune defence. This delicate balance is ensured by intrinsic or extrinsic immunoregulatory mechanisms.

The pro- and anti-tumor role of ILC2s.

Group 2 innate lymphoid cells (ILC2s) are critical for the initiation of type 2 inflammatory diseases. However, ILC2s are also involved in the establishment of the immune microenvironment during tumor development, growth and metastasization. In this context, ILC2s have been shown to be either tumor-suppressive or tumor-promoting according to the tumor type, the cytokine secreted and the other immune cells that are, in turn, recruited and/or activated.

Double Positive CD4CD8 T Cells Are Enriched in Urological Cancers and Favor T Helper-2 Polarization.

The immune system plays a central role in cancer development, showing both anti-tumor and pro-tumor activities depending on the immune cell subsets and the disease context. While CD8 T cells are associated with a favorable outcome in most cancers, only T helper type 1 (Th1) CD4 T cells play a protective role, in contrast to Th2 CD4 T cells. Double positive (DP) CD4CD8 T cells remain understudied, although they were already described in human cancers, with conflicting data regarding their role.

γδ T-cell subsets in HIV controllers: potential role of Tγδ17 cells in the regulation of chronic immune activation.

Objectives: HIV controllers (HICs) are rare HIV-infected individuals able to maintain undetectable viremia in the absence of antiretroviral treatment. Although HIV-specific cytotoxic T cells have been well deciphered in HIC, γδ T lymphocytes remain largely uncharacterized. The aim of this study was to analyse phenotypic and functional characteristics of γδ T cells and their relationship with immune activation, which remains abnormally elevated and associated with comorbidities in HICs.

Intravesical Ty21a Vaccine Promotes Dendritic Cells and T Cell-Mediated Tumor Regression in the MB49 Bladder Cancer Model.

Preclinical data show that intravesical instillation of Ty21a/Vivotif, a commercial vaccine against typhoid fever, is an effective alternative option to standard Bacillus Calmette-Guérin (BCG) immunotherapy for non-muscle-invasive bladder cancer (NMIBC). Here, we characterized the inflammatory effects of Ty21a on the bladder and investigated the immune mechanisms underlying tumor regression toward the use of this bacterial vaccine in NMIBC patients. MB49 bladder tumor-bearing mice had significantly improved survival after intravesical instillations of Ty21a doses of 10 to 10 colony-forming units.

Conventional and PD-L1-expressing Regulatory T Cells are Enriched During BCG Therapy and may Limit its Efficacy.

Unlabelled: The regulation of immune responses occurring during Bacillus Calmette-Guerin (BCG) therapy need to be better scrutinized in order to identify new targetable pathways for non-muscle invasive bladder cancer treatment. Immunoregulatory mechanisms have emerged as key players in various cancers. While T lymphocytes are crucial for the control of tumor growth, they often include regulatory subsets known to restrain their anti-tumor activity.

Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis.

Group 2 innate lymphoid cells (ILC2s) are involved in human diseases, such as allergy, atopic dermatitis and nasal polyposis, but their function in human cancer remains unclear. Here we show that, in acute promyelocytic leukaemia (APL), ILC2s are increased and hyper-activated through the interaction of CRTH2 and NKp30 with elevated tumour-derived PGD2 and B7H6, respectively. ILC2s, in turn, activate monocytic myeloid-derived suppressor cells (M-MDSCs) via IL-13 secretion.

ILC2-modulated T cell-to-MDSC balance is associated with bladder cancer recurrence.

Non-muscle-invasive bladder cancer (NMIBC) is a highly recurrent tumor despite intravesical immunotherapy instillation with the bacillus Calmette-Guérin (BCG) vaccine. In a prospective longitudinal study, we took advantage of BCG instillations, which increase local immune infiltration, to characterize immune cell populations in the urine of patients with NMIBC as a surrogate for the bladder tumor microenvironment. We observed an infiltration of neutrophils, T cells, monocytic myeloid-derived suppressor cells (M-MDSCs), and group 2 innate lymphoid cells (ILC2).

Immunoregulation of Dendritic Cell Subsets by Inhibitory Receptors in Urothelial Cancer.

Unlabelled: Blockade of inhibitory receptors (IRs) overexpressed by T cells can activate antitumor immune responses, resulting in the most promising therapeutic approaches, particularly in bladder cancer, currently able to extend patient survival. Thanks to their ability to cross-present antigens to T cells, dendritic cells (DCs) are an immune cell population that plays a central role in the generation of effective antitumor T-cell responses. While IR function and expression have been investigated in T cells, very few data are available for DCs.

Preclinical efficacy and safety of the Ty21a vaccine strain for intravesical immunotherapy of non-muscle-invasive bladder cancer.

Intravesical Bacillus-Calmette-Guérin (BCG) immunotherapy can reduce recurrence/progression of non-muscle-invasive bladder cancer (NMIBC), although significant adverse events and treatment failure argue for alternative options. Here, we examined whether another attenuated live vaccine, Vivotif/Ty21a, used since more than 30 y against typhoid fever, may be safely used intravesically to improve bladder-tumor treatment. Mice-bearing MB49 orthotopic bladder-tumors treated with intravesical Ty21a or BCG were compared for survival and bacteria recovery.

Interleukin-1 receptor antagonist, a biomarker of response to anti-TB treatment in HIV/TB co-infected patients.

Objectives: Despite the high frequency of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in human immunodeficiency virus (HIV)/TB co-infected patients, no diagnostic test is available. Here, we investigated whether monocyte/macrophage activation markers can predict TB-IRIS occurrence and if they are modulated by anti-TB treatment.

Methods: Frozen plasma was obtained from 127 HIV/TB co-infected adults naïve for antiretroviral therapy, enrolled in the CAMELIA trial, 36 of whom developed TB-IRIS.