Modification of the HLA-A*24:02 Peptide Binding Pocket Enhances Cognate Peptide-Binding Capacity and Antigen-Specific T Cell Activation.

The immunogenicity of a T cell Ag is correlated with the ability of its antigenic epitope to bind HLA and be stably presented to T cells. This presents a challenge for the development of effective cancer immunotherapies, as many self-derived tumor-associated epitopes elicit weak T cell responses, in part due to weak binding affinity to HLA. Traditional methods to increase peptide-HLA binding affinity involve modifying the peptide to reflect HLA allele binding preferences.

Coexisting Type 1 Autoimmune Pancreatitis and Mixed-type Intraductal Papillary Mucinous Neoplasm.

An 84-year-old man was referred to our hospital for a cystic lesion of the pancreatic head, swelling of the pancreatic tail and hilar biliary stricture, resulting in elevated liver enzyme levels. We suspected branch duct-type intraductal papillary mucinous neoplasm (IPMN) and type I autoimmune pancreatitis (AIP) associated with sclerosing cholangitis because of the high serum IgG4 levels. The main pancreatic duct on the tail side of the AIP lesion was moderately dilated.

CD1d expression in glioblastoma is a promising target for NKT cell-based cancer immunotherapy.

Glioblastoma is the most common and aggressive type of brain tumor with high recurrence and fatality rates. Although various therapeutic strategies have been explored, there is currently no effective treatment for glioblastoma. Recently, the number of immunotherapeutic strategies has been tested for malignant brain tumors.

Phase II study of α-galactosylceramide-pulsed antigen-presenting cells in patients with advanced or recurrent non-small cell lung cancer.

Background: Invariant natural killer T (iNKT) cells produce copious amounts of cytokines in response to specific glycolipid antigens such as α-galactosylceramide (αGalCer) presented by CD1d-expressing antigen-presenting cells (APCs), thus orchestrating other immune cells to fight tumors. Because of their ability to induce strong antitumor responses activated by αGalCer, iNKT cells have been studied for their application in cancer immunotherapy. In our previous phase I/II trial in non-small cell lung cancer (NSCLC) patients who had completed the standard treatment, we showed a relatively long median survival time without severe treatment-related adverse events.

Immunological features of a lung cancer patient achieving an objective response with anti-programmed death-1 blockade therapy.

The role of immune checkpoint inhibitors in metastatic lung cancer has been established in recent years and the pretherapeutic profiles of the tumor microenvironment in responders have been increasingly reported. The role of salvage surgery and the immune profiles of the posttherapeutic specimens in patients achieving an objective response have rarely been studied. We report a case of metastatic lung cancer treated by anti-programmed death-1 Ab followed by surgical resection.

Regulatory T cells induce CD4 NKT cell anergy and suppress NKT cell cytotoxic function.

Background: Due to the strong tumoricidal activities of activated natural killer T (NKT) cells, invariant NKT cell-based immunotherapy has shown promising clinical efficacy. However, suppressive factors, such as regulatory T cells (Tregs), may be obstacles in the use of NKT cell-based cancer immunotherapy for advanced cancer patients. Here, we investigated the suppressive effects of Tregs on NKT cells and the underlying mechanisms with the aim to improve the antitumor activities of NKT cells.

[The analysis of Th2 cell subsets in house dust mite allergic rhinitis patients after sublingual immunotherapy].

Th2 cells are well known to play important roles in allergic diseases including allergic rhinitis (AR). Meanwhile, the factors that induce and sustain the pathogenesis of AR remain unclear. The recent development of sublingual immunotherapy (SLIT) is expected to allow changes to the underlying pathogenesis of AR.

Sublingual administration of liposomes enclosing alpha-galactosylceramide as an effective adjuvant of allergen immunotherapy in a murine model of allergic rhinitis.

Background: Sublingual immunotherapy (SLIT) is an established efficacious approach for the treatment of allergic rhinitis (AR). However, SLIT requires a long administration period to establish stable and adequate responses. This study investigated the efficacy of the sublingual administration of an allergen with liposomes enclosing α-GalCer (α-GC-liposome) as a potential adjuvant in mice with AR.

Soluble factors derived from neuroblastoma cell lines suppress dendritic cell differentiation and activation.

Dendritic cells (DC) play a key role in the initiation of both antitumor immunity and immunological tolerance. It has been demonstrated that exposure to soluble factors produced by tumor cells modulates DC functions and induces tolerogenic DC differentiation. In this study, we investigated the effects of neuroblastoma cell line-derived soluble factors on DC differentiation.

Activated iNKT cells enhance the anti-tumor effect of antigen specific CD8 T cells on mesothelin-expressing salivary gland cancer.

Background: Salivary gland cancers are not sensitive to conventional radiotherapy or chemotherapy regimens. Therefore, the development of a new treatment strategy is of critical importance for improving the prognosis. We examined the expression of mesothelin molecules in salivary gland cancers and the efficacy of adoptive cell therapy based on mesothelin-specific chimeric antigen receptor transduced T cells.

Clinical Application of iNKT Cell-mediated Anti-tumor Activity Against Lung Cancer and Head and Neck Cancer.

Invariant natural killer T (iNKT) cells produce copious amounts of cytokines in response to T-cell receptor (TCR) stimulation by recognizing antigens such as α-galactosylceramide (α-GalCer) presented on CD1d; thus, orchestrating other immune cells to fight against pathogen infection and tumors. Because of their ability to induce strong anti-tumor responses and the convenience of their invariant TCR activated by a synthetic ligand, α-GalCer, iNKT cells have been intensively studied for application in immunotherapeutic approaches to treat cancer patients in the clinic. Here, we summarize the clinical trials of iNKT cell based immunotherapy for non-small cell lung cancer, and head and neck cancer.

Immunosuppressive property of submandibular lymph nodes in patients with head and neck tumors: differential distribution of regulatory T cells.

Objective: Different sensitizations and immune responses are thought to be induced in response to antigens at different mucosal sites between the oral floor and nose. The aim of this study was to investigate differences in the distributions of lymphocyte subsets in the submandibular (SM) and upper jugular (UJ) lymph nodes (LNs), which are supposed to be regional LNs of the oral floor and nasal mucosa, respectively. SMLNs and UJLNs were collected from patients with head and neck tumors who underwent surgical resection.

Invariant natural killer T infiltration in neuroblastoma with favorable outcome.

Background: Tumor immunity has been suggested to play a key role in clinical and biological behavior of neuroblastomas. Given that CD1-restricted invariant natural killer T (iNKT) cells enhance both innate and acquired tumor immunity, we investigated the expression of the iNKT-cell-specific T-cell receptor Vα24-Jα18 in neuroblastoma tissues and its correlation with clinical and biological characteristics.

Methods: Using real- time quantitative PCR, we quantified the expression of Vα24-Jα18 in untreated tumor samples from 107 neuroblastoma cases followed in our institution and analyzed the correlation between the presence of infiltrated iNKT cells and clinical characteristics or patients' outcome.

Frequency and proliferative response of circulating invariant natural killer T cells in pediatric patients with malignant solid tumors.

Background: Invariant natural killer T (iNKT) cells play an important role in tumor immunity, enhancing both innate and acquired immunity. We have previously shown the enhancement of antibody-dependent cellular cytotoxicity against neuroblastoma by activated iNKT cells. As a first step towards clinical application, we studied the frequency and proliferative response of circulating iNKT cells in children with and without cancer.

CD45RAFoxp3 regulatory T cells have a negative impact on the clinical outcome of head and neck squamous cell carcinoma.

Background: Although regulatory T cells (Tregs) are thought to play an important role in immune suppression, their clinical significance in head and neck squamous cell carcinoma (HNSCC) is unclear. A recent study reported Tregs could be divided into functional subsets based on the expression of CD45RA and Foxp3.

Method: The frequency of circulating Treg subsets was analyzed in patients with HNSCC and compared with the frequency in patients with benign tumors.

[Invariant NKT cell-based immunotherapy for lung cancer and head and neck cancer].

CD1d-restricted invariant natural killer T (iNKI) cells are the unique lymphocyte subpopu- lation that interacts with glycolipid via the invariant T cell receptor. Ligand activated iNKT cells produce a variety of cytokines, and thus bridging the innate and adaptive immune sys- tems. Since recent studies have highlighted iNKT cells to have potent anti-tumor effects, greater attention are being given to the development of iNKT cell-based immunotherapy for advanced solid tumors.

Blockade of programmed death-1/programmed death ligand pathway enhances the antitumor immunity of human invariant natural killer T cells.

The role of invariant natural killer T (iNKT) cells in antitumor immunity has been studied extensively, and clinical trials in patients with advanced cancer have revealed a prolonged survival in some cases. In recent years, humanized blocking antibodies against co-stimulatory molecules such as PD-1 have been developed. The enhancement of T cell function is reported to improve antitumor immunity, leading to positive clinical effects.

Invariant NKT cells are resistant to circulating CD15+ myeloid-derived suppressor cells in patients with head and neck cancer.

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature and progenitor myeloid cells with an immunosuppressive role in various types of cancer, including head and neck squamous cell carcinoma (HNSCC). However, the effect on the host immune system, especially on invariant NKT (iNKT) cells with potent anti-tumor activity, remains unclear. In this study, we investigated the effects of circulating MDSC subsets on the peripheral lymphocytes of patients with head and neck tumors.

[A Clinical Study of a Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma of Salivary Glands].

Malignant lymphoma involving the salivary glands is a rare entity that accounts for only 1 to 4% of all salivary gland tumors. We have analyzed the clinical features of MALT lymphoma of the salivary glands in 7 patients whom we have treated in the past 10 years, including data from 43 patients in the literature. The most common symptom was persistent or progressive swelling of the salivary glands without pain or facial palsy.

[The efficacy of superselective intra-arterial chemo-radiotherapy for cervical neck lymph node metastases].

We report herein on 32 cases of head and neck carcinoma with cervical lymph node metastases treated by radiotherapy and concomitant intraarterial cisplatin (RADPLAT) from April 2009 to May 2013. N3 cases revealed residual disease of the cervical lymph nodes in 7/9 cases. Among the 22 patients excluding N1 and N3 cases, the pathological CR rate was 63.

[Experience of two cases of tetanus without a clear history of trauma].

Tetanus develops following inoculation of damaged human tissue with Clostridium tetani which transforms into a vegetative rod-shaped bacterium and produces the tetanospasmin. Usually we make a diagnosis of tetanus based on typical symptoms and history of trauma. But, when patients have no noticeable history of trauma, we have to diagnose tetanus on the basis of the clinical course and symptoms.

[A clinical study on 8 cases of sarcoidosis with a cervical mass as a symptom].

Sarcoidosis is a multiorgan granulomatous disease of unknown origin, which frequently involves the lung and the eyes. It is rare that sarcoidosis causes cervical lymphadenopathy and a chronic continuous salivary gland swelling. In the present study, we examined how to diagnose sarcoidosis in patients complaining of a cervical mass and its clinical presentation according to 8 cases which we experienced.

Histopathological study of lymph node lesions in the acute phase of Kawasaki disease.

Aims:   To review the histopathological features of cervical LNs, and to clarify the changes in extracervical LNs, in acute Kawasaki disease (KD).

Methods And Results:   The samples were obtained from 33 patients with acute-phase KD. We divided the LNs into those in the neck (n = 23) and those located elsewhere (n = 26), and investigated them histologically.

Primary cardiac synovial sarcoma: a case report and literature review.

Primary cardiac synovial sarcoma is a rare disease. A 51-year-old man visited our hospital with the chief complaint of palpitations and shortness of breath while exercising. Copious bloody pericardial effusion and a multicystic intrapericardial tumor were detected.