Drift of the HIV-1 envelope glycoprotein gp120 toward increased neutralization resistance over the course of the epidemic: a comprehensive study using the most potent and broadly neutralizing monoclonal antibodies

Extending our previous analyses to the most recently described broadly neutralizing monoclonal antibodies (bNAbs) we confirm a drift of HIV-1 clade B variants over two decades toward higher resistance to bNAbs targeting almost all the identified gp120 neutralizing epitopes. In contrast, the sensitivity to bNAbs targeting the gp41 MPER remained stable, suggesting a selective pressure on gp120 preferentially. Despite this evolution, selected combinations of bNAbs remain capable to neutralize efficiently most of the circulating variants

Listeria monocytogenes-associated respiratory infections: a study of 38 consecutive cases

International audienceObjectives: Listeria monocytogenes (Lm) is a foodborne human pathogen responsible for severe infections, including septicaemia, neurolisteriosis, and maternalefoetal and focal infections. Little is known about Lm-associated respiratory tract or lung infections. Methods: We conducted a retrospective study of culture-proven cases of Lm pleural infections and pneumonia Results: Thirty-eight consecutive patients with pleural infection (n ¼ 32), pneumonia (n ¼ 5), or both (n ¼ 1) were studied; 71% of these were men. Median age was 72 (range 29e90). Two patients presented with concomitant neurolisteriosis. All patients but one reported at least one immunosuppressive condition (97%), with a median number of 2 (range 0e5), including 29% (8/28) with current exposure to immunosuppressive therapy and 50% (17/34) with ongoing neoplasia; 75% (21/28) reported previous pleural or pulmonary disease. Antibiotic therapy mostly consisted in amoxicillin (72%) associated with aminoglycoside in 32%. Chest-tube drainage was performed in 7/19 patients with empyema (37%); 25% of the patients (7/30) required intensive care management. In-hospital mortality reached 35% and occurred after a median time interval of 4 days (range 1e33 days). Three patients had recurrence of empyema (time interval of 1 week to 4 months after treatment completion). Altogether, only 13/31 patients (42%) diagnosed with Lm respiratory infection experienced an uneventful outcome at 2-year follow-up. Conclusion: Lm is a rare but severe cause of pneumonia and pleural infection in older immunocom-promised patients, requiring prompt diagnosis and adequate management and follow-up

Projet GELOCOM

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Evolution of Metastases in Space and Time under Immune Selection.

We examined how the immune microenvironment molds tumor evolution at different metastatic organs in a longitudinal dataset of colorectal cancer. Through multiplexed analyses, we showed that clonal evolution patterns during metastatic progression depend on the immune contexture at the metastatic site. Genetic evidence of neoantigen depletion was observed in the sites with high Immunoscore and spatial proximity between Ki67 tumor cells and CD3 cells. The immunoedited tumor clones were eliminated and did not recur, while progressing clones were immune privileged, despite the presence of tumor-infiltrating lymphocytes. Characterization of immune-privileged metastases revealed tumor-intrinsic and tumor-extrinsic mechanisms of escape. The lowest recurrence risk was associated with high Immunoscore, occurrence of immunoediting, and low tumor burden. We propose a parallel selection model of metastatic progression, where branched evolution could be traced back to immune-escaping clones. The findings could inform the understanding of cancer dissemination and the development of immunotherapeutics