Senescent CD8+ T cells acquire NK cell-like innate functions to promote antitumor immunity.

It has been suggested that aging of the immune system (immunosenescence) results in a decline in the acquired immune response, which is associated with an increase in age-related tumorigenesis. T-cell senescence plays a critical role in immunosenescence and is involved in the age-related decline of the immune function, which increases susceptibility to certain cancers. However, it has been shown that CD8+ T cells with the senescent T-cell phenotype acquire an natural killer (NK) cell-like function and are involved in tumor elimination. Therefore, the role of senescent CD8+ T cells in tumor immunity remains to be elucidated. In this study, we investigated the role of senescent CD8+ T cells in tumor immunity. In a murine model of transferred with B16 melanoma, lung metastasis was significantly suppressed in aged mice (age ≥30 weeks) in comparison to young mice (age 6-10 weeks). We evaluated the cytotoxic activity of CD8+ T cells in vitro and found that CD8+ T cells from aged mice activated in vitro exhibited increased cytotoxic activity in comparison to those from young mice. We used Menin-deficient effector T cells as a model for senescent CD8+ T cells and found that cytotoxic activity and the expression of NK receptors were upregulated in Menin-deficient senescent CD8+ T cells. Furthermore, Menin-deficient CD8+ T cells can eliminate tumor cells in an antigen-independent manner. These results suggest that senescent effector CD8+ T cells may contribute to tumor immunity in the elderly by acquiring NK-like innate immune functions, such as antigen-independent cytotoxic activity.

The histone demethylase Utx controls CD8+ T-cell-dependent antitumor immunity via epigenetic regulation of the effector function.

CD8+ T cells play a central role in antitumor immune responses. Epigenetic gene regulation is essential to acquire the effector function of CD8+ T cells. However, the role of Utx, a demethylase of histone H3K27, in antitumor immunity remains unclear. In this study, we examined the roles of Utx in effector CD8+ T-cell differentiation and the antitumor immune response. In a murine tumor-bearing model, an increased tumor size and decreased survival rate were observed in T-cell-specific Utx KO (Utx KO) mice compared with wild-type (WT) mice. The number of CD8+ T cells in tumor-infiltrating lymphocytes (TILs) was significantly decreased in Utx KO mice. We found that the acquisition of effector function was delayed and attenuated in Utx KO CD8+ T cells. RNA sequencing revealed that the expression of effector signature genes was decreased in Utx KO effector CD8+ T cells, while the expression of naïve or memory signature genes was increased. Furthermore, the expression of Cxcr3, which is required for the migration of effector CD8+ T cells to tumor sites, was substantially decreased in Utx KO CD8+ T cells. These findings suggest that Utx promotes CD8+ T-cell-dependent antitumor immune responses partially through epigenetic regulation of the effector function.

[Anesthetic Management with V-V ECMO in a Patient with Severe Tracheal Stenosis].

We here report a case in which tracheal stent insertion was performed using veno-venous extracorporeal membrane oxygenation (V-V ECMO). A 78-year-old man with severe tracheal stenosis due to thyroid cancer was suffering from dyspnea at rest. Computed tomography showed that the narrowest caliber of the trachea was 1.5 mm in diameter at 5 cm below the level of the vocal cords. Femoro-femoral V-V ECMO was established without hemodynamic instability. General anesthesia was induced with propofol 70 mg and fentanyl 50 µg and was maintained with propofol 150-200 mg x hr(-1) and remifentanil 0.3-0.5 mg x hr(-1) using target-controlled infusion devices. Mask ventilation was possible, and the trachea could be intubated. A rigid bronchoscope was advanced to the stenosis site after removing the endotracheal tube. Manual ventilation via a side port of the uncuffed bronchoscope could not achieve normal inflation of the both chest walls because of air leaks. Throughout the procedures, hypoxemia and hypercapnia could be prevented by manual ventilation supplemented with low-flow V-V ECMO. Stent implantation was performed successfully. This case suggests that V-V ECMO is useful for providing supplementary oxygenation and carbon dioxide elimination when adequate ventilation cannot be provided during tracheal stent implantation.