Tumor regression after combination of radiation and PD-1 antibody nivolumab treatment in a patient with metastatic mediastinal leiomyosarcoma: a case report.

The PD-1/PD-L1 axis is characterized as an important checkpoint of immune activation, particularly through negatively regulating T cell function. Although accumulated evidence has demonstrated the patients with some types of tumor benefit from blockade of PD-1/PD-L1 signaling pathway, the possible synergistic effect of combination of radiotherapy and anti-PD-1/PD-L1 antibody still need to be explored. Here, we report a case of patient who was diagnosed with metastatic mediastinal leiomyosarcoma and treated by combination of local radiotherapy and anti-PD-1 antibody nivolumab. Remarkable tumor regression was observed at both the irradiated focus and distant metastatic sites 2 months later after combined treatment. The patient has tumor mutational burden (8.7 somatic mutations/Mb) and positive PD-L1 expression. The increased circulating lymphocytes suggest induced activation of immune response after combination treatment. Free disease progression has reached one and a half years as far.

Research progress of the application of immune checkpoints in tumor radiotherapy / 中华放射医学与防护杂志

Radiation could induce DNA damage,cell death,and changes of tumor phenotype and tumor microenvironment leading to the regulation of immune response.Immune checkpoint signaling pathways are involved in the immune tolerance of anti-microorganism responses and thus limit tissue damage.In the anti-tumor immune response,these pathways are associated with anti-functional activation of specific cytotoxic T cells and also enhance the inhibition effect of immune response,which always result in immune escape.Blockade of the immune checkpoint signaling pathways benefits to the anti-tumor inmune responses and could delay tumor progress.As a result,the combination treatment of radiotherapy and immune checkpoint biockade has attracted more attentions in clinical application.This paper reviews the recent research progresses in the radiation effect of immune system,the regulation of immune checkpoints and the combination treatment of radiotherapy and immune checkpoint blockade in tumor therapy,trying to arouse some new clues in cancer therapy.

Disulfide-stabilized diabody antiCD19/antiCD3 exceeds its parental antibody in tumor-targeting activity.

BACKGROUND: A diabody is a bispecific antibody that is capable of recruiting a polyclonal T cell to antibody target-expressing tumor cells. However, the two chains of diabodies tend to dissociate because they are integrated non-covalently. Therefore, it is necessary to remodel the diabody to increase its stability in order to enhance the antitumor activity. METHODS: We constructed an antiCD3×antiCD19 diabody with one binding site for the T cell antigen receptor (TCRCD3) and the other for the B cell-specific antigen (CD19) by recombinant gene engineering technology. Cysteine residues were introduced into the V domains of the anti-CD3 segment. The stability and cytotoxicity of the two diabodies were compared in vitro and vivo. RESULTS: The disulfide-stabilized (ds) diabodies produced by Escherichia coli were secreted with high yields in a fully active form without a decrease in affinity. Compared with the parental diabody, the disulfide-stabilized (ds) diabody proved more stable in vitro and in vivo without reducing binding affinity. Both were able to effectively eliminate human lymphoma Raji cells by redirecting T lymphocytes in vitro and in vivo, but the ds diabody was more effective in inhibiting the growth of xenografts transplanted in BALB/C nude mice. CONCLUSION: The antiCD3×antiCD19 ds diabody is more suitable for a controlled polyclonal T cell therapy of human CD19-positive B cell malignancies than its parental diabody.

The role of autophagy in cell survival and tumor development / 中国药理学通报

Autophagy occurs in all types of eukaryotic cells, which has a rigid connection with the normal or abnormal development of cells and is associated with many diseases. There're lots of molecular control elements and multiple signaling pathways involved in regulating autophagy. As a form of type Ⅱ programmed cell death, autophagy participates in maintaining cell homeostasis and pathogenesis of various of diseases through interacting with apoptotic pathway. Recent studies show that autophagy has effects on the occurrence and development of tumor cells through influencing on cell cycle, apoptosis-associated factors and angiogenesis.