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Uveal melanoma (UM) is the most common cancer of the eye. The loss of chromosome 3 (M3) is associated with a high risk of metastases. M3 tumors are more infiltrated by T-lymphocytes than low-risk disomic-3 (D3) tumors, contrasting with other tumor types in which T cell infiltration correlates with better prognosis. Whether these T cells represent an antitumor response and how these T cells would be primed in the eye are both unknown. Herein, we characterized the T cells infiltrating primary UMs. CD8+ and Treg cells were more abundant in M3 than in D3 tumors. CD39+PD-1+CD8+ T cells were enriched in M3 tumors, suggesting specific responses to tumor antigen (Ag) as confirmed using HLA-A2:Melan-A tetramers. scRNAseq-VDJ analysis of T cells evidenced high numbers of proliferating CD39+PD1+CD8+ clonal expansions, suggesting in situ antitumor Ag responses. TCRseq and tumor-Ag tetramer staining characterized the recirculation pattern of the antitumor responses in M3 and D3 tumors. Thus, tumor-Ag responses occur in localized UMs, raising the question of the priming mechanisms in the absence of known lymphatic drainage., (© 2024 Lucibello et al.)

Background: The mechanisms regulating CD8 + T cell migration to nonlymphoid tissue during inflammation have not been fully elucidated, and the migratory properties of effector memory CD8 + T cells that re-express CD45RA (TEMRA CD8 + T cells) remain unclear, despite their roles in autoimmune diseases and allotransplant rejection., Methods: We used single-cell proteomic profiling and functional testing of CD8 + T cell subsets to characterize their effector functions and migratory properties in healthy volunteers and kidney transplant recipients with stable or humoral rejection., Results: We showed that humoral rejection of a kidney allograft is associated with an accumulation of cytolytic TEMRA CD8 + T cells in blood and kidney graft biopsies. TEMRA CD8 + T cells from kidney transplant recipients exhibited enhanced migratory properties compared with effector memory (EM) CD8 + T cells, with enhanced adhesion to activated endothelium and transmigration in response to the chemokine CXCL12. CXCL12 directly triggers a purinergic P2×4 receptor-dependent proinflammatory response of TEMRA CD8 + T cells from transplant recipients. The stimulation with IL-15 promotes the CXCL12-induced migration of TEMRA and EM CD8 + T cells and promotes the generation of functional PSGL1, which interacts with the cell adhesion molecule P-selectin and adhesion of these cells to activated endothelium. Although disruption of the interaction between functional PSGL1 and P-selectin prevents the adhesion and transmigration of both TEMRA and EM CD8 + T cells, targeting VLA-4 or LFA-1 (integrins involved in T cell migration) specifically inhibited the migration of TEMRA CD8 + T cells from kidney transplant recipients., Conclusions: Our findings highlight the active role of TEMRA CD8 + T cells in humoral transplant rejection and suggest that kidney transplant recipients may benefit from therapeutics targeting these cells., (Copyright © 2022 by the American Society of Nephrology.)

Approximately one in ten elderly people living at home is undernourished. Undernutrition is, among other things, a factor in loss of autonomy and hospitalization. If identified and treated early, it can be "cured". This is the principle behind the D-Nut program, which has been tested in the Pays de la Loire region. When a registered nurse (Idel) visits an elderly patient during a treatment, she can perform a nutritional test via a mobile application. Once the patient has agreed, a four- to six-month assessment and multi-professional management phase is implemented in the patient's home, coordinated by the nurse., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

In anaerobic infections, the relationship between clinical failure and antibiotic resistance is difficult to demonstrate, especially in mixed anaerobic-aerobic infections. Single isolates of anaerobes in cases of bacteraemia revealed that treatment failures were due to inappropriate therapy. We review here cases, where the empiric treatment was unsuccessful due to resistance of anaerobic bacteria to the administered agents and where the change of the antibiotic allowed the patients to be cured. Many therapeutic failures could be linked to the lack of timely detection of resistance, including heteroresistance of the anaerobes. Disk diffusion or Etest methodology may be suitable, at least for rapidly growing anaerobes, to detect both resistance and heteroresistance to antibiotics widely used for empirical therapy., Competing Interests: Declaration of competing interest We declare no conflict of interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)