PD-1 blockade therapy promotes infiltration of tumor-attacking exhausted T cell clonotypes

PD-1 blockade exerts clinical efficacy against various types of cancer by reinvigorating T cells that directly attack tumor cells (tumor-specific T cells) in the tumor microenvironment (TME), and tumor-infiltrating lymphocytes (TILs) also comprise nonspecific bystander T cells. Here, using single-cell sequencing, we show that TILs include skewed T cell clonotypes, which are characterized by exhaustion (T-ex) or nonexhaustion signatures (Tnon-ex). Among skewed clonotypes, those in the T-ex, but not those in the Tnon-ex, cluster respond to autologous tumor cell lines. After PD-1 blockade, non-preexisting tumor-specific clonotypes in the T-ex cluster appear in the TME. Tumor-draining lymph nodes (TDLNs) without metastasis harbor a considerable number of such clonotypes, whereas these clonotypes are rarely detected in peripheral blood. We propose that tumor-infiltrating skewed T cell clonotypes with an exhausted phenotype directly attack tumor cells and that PD-1 blockade can promote infiltration of such T-ex clonotypes, mainly from TDLNs

Efficient oxidation of alcohols electrochemically mediated by azabicyclo-N-oxyls

Preparation of azabicyclo-N-oxyls and the electrochemical oxidation of alcohols using them as mediators have been exploited. This oxidation was applicable to a transformation of sterically hindered secondary alcohols into the corresponding ketones in high yields

Loxodromic Eisenstein Series for Cofinite Kleinian Groups (Automorphic Forms, Automorphic L-Functions and Related Topics)

We introduce an Eisenstein series associated to a loxodromic element of cofinite Kleinian groups, named the loxodromic Eisenstein series, and study its fundamental properties. We also establish the precise spectral expansion associated to the Laplace-Beltrami operator and derive the analytic continuation with the location of the possible poles and their residues. In addition, we study the asymptotic behavior of the loxodromic Eisenstein series for a degenerating sequence of fimite volume three-dimensional hyperbolic manifolds

LOXODROMIC EISENSTEIN SERIES THROUGH DEGENERATION

The loxodromic Eisenstein series is defined for a loxodromic element of cofinite Kleinian groups. It is the analogue of the ordinary Eisenstein series associated to cusps. We study the asymptotic behavior of the loxodromic Eisenstein series for degenerating sequences of three-dimensional hyperbolic manifolds of finite volume. In particular, we prove that if the loxodromic element corresponds to the degenerating geodesic, then the associated loxodromic Eisenstein series converges to the ordinary Eisenstein series associated to the newly developing cusp on the limit manifold

Superior vena cava syndrome caused by mediastinal recurrence of breast cancer with a 13-year disease-free interval: A case report

　Superior vena cava syndrome (SVCS) is an oncological emergency. Lung cancer is the most causative malignancy. In contrast, breast cancer rarely causes SVCS. We report a case in which SVCS was caused by mediastinal lymph node metastasis of breast cancer. The patient was a 60-year-old woman who had undergone breast-conserving therapy at another hospital 13 years previously. Her breast cancer was early stage T1a(5mm)N0M0; Stage IA), and Luminal type (HER2 negative). She had received adjuvant hormone therapy, but dropped out of treatment two years and six months later. Recently, she had developed cough and face edema, and her extrajugular vein was swollen. CT revealed swollen mediastinal and supraclavicular lymph nodes, lung nodules, pericardial effusion, right pleural fluid, and stenosis of the superior vena cava (SVC). She was diagnosed with recurrent breast cancer with SVCS due to mediastinal LN swelling. A core needle biopsy of a supraclavicular lymph node revealed metastasis; the diagnosis was luminal HER2 positive breast cancer. We initiated treatment with radiotherapy for the mediastinal lymph nodes, and then started hormone therapy and anti-HER2 therapy. These therapies provided relief from her symptoms. She is currently alive and continuing hormone therapy and anti-HER2 therapy. In cases of SVCS due to malignancy, the biopsy findings should be taken into account when possible. An accurate diagnosis is extremely important for the suitable treatment of SVCS, especially in cases caused by malignancy