In der Vergangenheit erwiesen sich Anti-PD-1- sowie Anti-PD-L1-Therapien bei Behandlung des metastasierten nichtkleinzelligen Lungenkarzinoms (NSCLC) als effektiv. Leider sind die Ansprechraten nach wie vor unbefriedigend. J. Huang et al. haben untersucht, ob Ginseng-Polysaccharide (GP) das Ansprechen auf eine Therapie mit monoklonalen αPD-1-Antikörpern mittels einer Modulation Darmmikrobiota v...

BACKGROUND Studies combining immune checkpoint inhibitors with external beam radiation have shown a therapeutic advantage over each modality alone. The purpose of these works is to evaluate the potential of targeted delivery of high LET radiation to the tumor microenvironment via an immune checkpoint inhibitor. METHODS The impact of protein concentration on the distribution of 111In-DTPA-anti...

PURPOSE Immunomodulatory drugs differ in mechanism-of-action from directly cytotoxic cancer therapies. Identifying factors predicting clinical response could guide patient selection and therapeutic optimization. EXPERIMENTAL DESIGN Patients (N = 41) with melanoma, non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), colorectal carcinoma, or castration-resistant prostate cancer w...

BACKGROUND Programmed death-1 (PD-1), a member of the CD28 family, has been identified. PD-1 is involved in the negative regulation of some immune responses. We evaluated the role of PD-ligand 1 (PD-L1) in graft arterial disease (GAD) of cardiac allografts and in smooth muscle cells (SMCs). METHODS AND RESULTS C57BL/6 murine hearts were transplanted into B6.C-H2KhEg mice for examination...

Blocking the programmed cell death 1 (PD-1) pathway with monoclonal antibodies has shown promising antitumor responses in clinical trials, with less toxicity than has been seen with prior immune therapies such as interleukin 2 and ipilimumab. Pembrolizumab, an anti-PD-1 antibody, recently gained US Food and Drug Administration (FDA) accelerated approval for the treatment of patients with ipilim...

PD-1 negatively regulates CD8(+) cytotoxic T lymphocytes (CTL) cytotoxicity and anti-tumor immunity. However, it is not fully understood how PD-1 expression on CD8(+) CTL is regulated during anti-tumor immunotherapy. In this study, we have identified that the ADAP-SKAP55 signaling module reduced CD8(+) CTL cytotoxicity and enhanced PD-1 expression in a Fyn-, Ca(2+)-, and NFATc1-dependent manner...

Purpose: Immunomodulatory drugs differ in mechanism-of-action from directly cytotoxic cancer therapies. Identifying factors predicting clinical response could guide patient selection and therapeutic optimization. Experimental Design: Patients (N 1⁄4 41) with melanoma, non–small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), colorectal carcinoma, or castration-resistant prostate cancer...

We focused on the ability of the pan-histone deacetylase (HDAC) inhibitors AR42 and sodium valproate to alter the immunogenicity of melanoma cells. Treatment of melanoma cells with HDAC inhibitors rapidly reduced the expression of multiple HDAC proteins as well as the levels of PD-L1, PD-L2 and ODC, and increased expression of MHCA. In a cell-specific fashion, melanoma isolates released the imm...

Immune checkpoint therapy is one of the most promising immunotherapeutic methods that are likely able to give rise durable treatment response for various cancer types. Despite much progress in past decade, there still critical open questions with particular regards quantifying and predicting efficacy potential optimal regimens combining different immune blockades. To shed light on this issue, h...