Rationale for LDH-targeted cancer immunotherapy.

Immunotherapies have significantly improved the survival of patients in many cancers over the last decade. However, primary and secondary resistances are encountered in most patients. Unravelling resistance mechanisms to cancer immunotherapies is an area of active investigation.

Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer.

Aside from PD-L1 expression, biomarkers of response to immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) are needed. In a previous retrospective analysis, we documented that fecal Akkermansia muciniphila (Akk) was associated with clinical benefit of ICI in patients with NSCLC or kidney cancer. In the current study, we performed shotgun-metagenomics-based microbiome profiling in a large cohort of patients with advanced NSCLC (n = 338) treated with first- or second-line ICIs to prospectively validate the predictive value of fecal Akk.

gen. nov., sp. nov., a new bacterium isolated from the human gut microbiota.

An anaerobic facultative Gram-stain positive bacterium was isolated from human gut microbiota. Strain Marseille-P5551 was considered to be a new genus within the phylum , as it exhibits a 91.87% similarity level with (NR_117129.

Trial watch : the gut microbiota as a tool to boost the clinical efficacy of anticancer immunotherapy.

Accumulating evidence demonstrates the decisive role of the gut microbiota in determining the effectiveness of anticancer therapeutics such as immunogenic chemotherapy or immune checkpoint blockade in preclinical tumor models, as well as in cancer patients. In synthesis, it appears that a normal intestinal microbiota supports therapeutic anticancer responses, while a dysbiotic microbiota that lacks immunostimulatory bacteria or contains overabundant immunosuppressive species causes treatment failure. These findings have led to the design of clinical trials that evaluate the capacity of modulation of the gut microbiota to synergize with treatment and hence limit tumor progression.

T-cell bispecific antibodies in node-positive breast cancer: novel therapeutic avenue for MHC class I loss variants.

Background: Tumor-infiltrating lymphocytes (TILs) represent a prognostic factor for survival in primary breast cancer (BC). Nonetheless, neoepitope load and TILs cytolytic activity are modest in BC, compromising the efficacy of immune-activating antibodies, which do not yet compete against immunogenic chemotherapy.

Patients And Methods: We analyzed by functional flow cytometry the immune dynamics of primary and metastatic axillary nodes [metastatic lymph nodes (mLN)] in early BC (EBC) after exposure to T-cell bispecific antibodies (TCB) bridging CD3ε and human epidermal growth factor receptor 2 (HER2) or Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 (CEACAM5), before and after chemotherapy.

Correction: Absence of anti-hypocretin receptor 2 autoantibodies in post pandemrix narcolepsy cases.

[This corrects the article DOI: 10.1371/journal.pone.

Autoimmunity to hypocretin and molecular mimicry to flu in type 1 narcolepsy.

Type 1 narcolepsy (T1N) is caused by hypocretin/orexin (HCRT) neuronal loss. Association with the HLA DQB1*06:02/DQA1*01:02 (98% vs. 25%) heterodimer (DQ0602), T cell receptors (TCR) and other immune loci suggest autoimmunity but autoantigens are unknown.

Absence of anti-hypocretin receptor 2 autoantibodies in post pandemrix narcolepsy cases.

Background: A recent publication suggested molecular mimicry of a nucleoprotein (NP) sequence from A/Puerto Rico/8/1934 (PR8) strain, the backbone used in the construction of the reassortant strain X-179A that was used in Pandemrix® vaccine, and reported on anti-hypocretin (HCRT) receptor 2 (anti-HCRTR2) autoantibodies in narcolepsy, mostly in post Pandemrix® narcolepsy cases (17 of 20 sera). In this study, we re-examined this hypothesis through mass spectrometry (MS) characterization of Pandemrix®, and two other pandemic H1N1 (pH1N1)-2009 vaccines, Arepanrix® and Focetria®, and analyzed anti-HCRTR2 autoantibodies in narcolepsy patients and controls using three independent strategies.

Methods: MS characterization of Pandemrix® (2 batches), Arepanrix® (4 batches) and Focetria® (1 batch) was conducted with mapping of NP 116I or 116M spectrogram.

Autoimmunity in narcolepsy.

Purpose Of Review: Summarize the recent findings in narcolepsy focusing on the environmental and genetic risk factors in disease development.

Recent Findings: Both genetic and epidemiological evidence point towards an autoimmune mechanism in the destruction of orexin/hypocretin neurons. Recent studies suggest both humoral and cellular immune responses in the disease development.

Kinetic theory of diffusion-limited nucleation.

We examine binary nucleation in the size and composition space {R,c} using the formalism of the multivariable theory [N. V. Alekseechkin, J.

Comparison of Pandemrix and Arepanrix, two pH1N1 AS03-adjuvanted vaccines differentially associated with narcolepsy development.

Narcolepsy onset in children has been associated with the 2009 influenza A H1N1 pandemic and vaccination with Pandemrix. However it was not clearly observed with other adjuvanted pH1N1 vaccines such as Arepanrix or Focetria. Our aim was to characterize the differences between Pandemrix and Arepanrix that might explain the risk for narcolepsy after Pandemrix vaccination using 2D-DIGE and mass spectrometry (MS).

Allergen-specific CD4+ T cell responses in peripheral blood do not predict the early onset of clinical efficacy during grass pollen sublingual immunotherapy.

Background: Surrogate biomarkers of efficacy are needed in support of allergen-specific immunotherapy.

Objective: The aim of this study was to relate changes in peripheral CD4(+) T cell responses to clinical efficacy during sublingual immunotherapy (SLIT).

Methods: Allergen-specific CD4(+) T cell responses were assessed in peripheral blood mononuclear cells (PBMCs) from 89 grass pollen-allergic individuals enrolled in a double-blind placebo-controlled SLIT study conducted in an allergen exposure chamber (ClinicalTrials.

Generic drug prescriptions following hospital discharge: a prospective study in France.

Aims: Systematic generic prescription at discharge could reduce confusion on drug-name usage, decrease commercial influence on medicine, and reduce drug-related expenditures. This study aimed to analyze generic drug prescriptions at discharge from hospital and to estimate the potential savings associated with a total substitution policy (substitution of every substitutable drug for its cheapest generic counterpart).

Methods: Drug prescriptions before admission and at discharge of all patients from three medical units of a university hospital were prospectively collected for five weeks without informing prescribers.

Comparison between major histocompatibility complex class II tetramer staining and surface expression of activation markers for the detection of allergen-specific CD4⁺ T cells.

Background: Major histocompatibility complex (MHC) class II tetramers (tetramers) allow to detect allergen-specific CD4(+) T cells at a single-cell level. Limits to this technology include HLA restriction and the need to identify immunodominant T cell epitopes.

Objective: Assessing the expression of various activation markers following allergen stimulation to replace tetramer staining.

Inorganic arsenic alters expression of immune and stress response genes in activated primary human T lymphocytes.

Inorganic arsenic, a carcinogenic environmental contaminant, exerts immunosuppressive effects on human T lymphocytes. In particular, interleukin-2 (IL2) secretion and T cell proliferation are reduced when peripheral blood mononuclear cells (PBMC) from individuals chronically exposed to arsenic are stimulated ex vivo with lectins such as phytohemaglutinin (PHA). However, it is not clear whether the metalloid directly acts on T cells or blocks monocyte-dependent accessory signals activated by PHA.

Distinct characteristics of seasonal (Bet v 1) vs. perennial (Der p 1/Der p 2) allergen-specific CD4(+) T cell responses.

Background: A better understanding of allergen-specific CD4(+) T cell responses is needed to help improving immunological therapies. Objective To compare CD4(+) T cell responses against seasonal (Bet v 1) and perennial (Der p 1, Der p 2) allergens.

Methods: Major histocompatibility complex class II peptide tetramers were engineered to monitor allergen-specific T cell responses.

Molecular variability of group 1 and 5 grass pollen allergens between Pooideae species: implications for immunotherapy.

Background: Differences between major allergens from distinct grass species remain to be investigated, both in terms of structure and antigenicity.

Methods: Group 1 and 5 allergens purified from five common Pooideae species were analysed by mass spectrometry (MS). Major histocompatibility complex (MHC) class II-restricted T cell epitopes were identified using predictive algorithms and human leucocyte antigen (HLA)-binding assays.