Immunotherapy has shown encouraging results in various tumor types. This progress is largely attributed to identification of new immune-based targets, based on our enhanced understanding of tumor immunology and the tumor microenvironment. Many kinds of immune-modulating therapies have been demonstrated to the treatment of GI cancers, nonspecific interleukin-2 activated lymphocytes, tumor-reactive CD8+ tumor infiltrating T lymphocyte, or tumor associated antigen derived peptides. These immunotherapy represented a certain efficacy, but not durable objective responses. The efficacy of immunotherapy was given everyone’s confidence after the coming of immune checkpoint inhibitors which was selected for “Breakthrough of the year 2013”in Science, and immunotherapy is now going to the major stream of the treatment against GI cancer. In this article, we review the immunotherapy of GI malignancies, including cell therapy, peptide vaccine, and combination immunotherapy beyond immune checkpoint inhibitors.

Advanced age affects various tissue-specific stem cells and decreases their regenerative ability. We therefore examined whether aging affected the quantity and quality of cardiac stem cells using cells obtained from 26 patients of various ages（from 2 to 83 years old）．We collected fresh right atria and cultured cardiosphere-derived cells（CDCs），which are a type of cardiac stem cell. Then we investigated growth rate, senescence, DNA damage, and the growth factor production of CDCs. All samples yielded a sufficient number of CDCs for experiments and the cellular growth rate was not obviously associated with age. The expression of senescence-associated β-galactosidase and the DNA damage marker, γH2AX, showed a slightly higher trend in CDCs from older patients（?65 years）．The expression of VEGF, HGF, IGF-1, SDF-1, and TGF-β varied among samples, and the expression of these beneficial factors did not decrease with age. An in vitro angiogenesis assay also showed that the angiogenic potency of CDCs was not impaired, even in those from older patients. Our data suggest that the impact of age on the quantity and quality of CDCs is quite limited. These findings have important clinical implications for autologous stem cell transplantation in elderly patients.

Neuromyelitis optica（NMO）is a first CNS autoimmune disease in which pathogenic autoantibodies against a specific tissue target molecule, aquaporin 4（AQP4），has been identified. The blood-brain barrier（BBB）breakdown and subsequent entry of AQP4-IgG into the brain are considered to be an important step for the development of NMO. We hypothesized that a distince endothelial cell-specific antibodies, other than AQP-IgG, may be presented in sera from NMO patients and promote transit of AQP4-IgGs across the BBB. First, we identified a monoclonal recombinant antibody（rAb）from CSF plasma blasts in NMO patients, which can bind and activate the human brain microvascular endothelial cells. Next, we identified the glucose-regulated protein 78（GRP78）as the antigenic targets of NMO-rAb using unbiased membrane proteomics. Last, we observed that incubation or administration of this GRP78 specific rAb can increase BBB permeability in vitro and in vivo. The development of antibody-based therapeutics against β-amyloid protein for Alzheimer disease and α-synuclein protein for Parkinson disease now have become developing area in the drug industry, but BBB limits the utility of antibody therapeutics for these CNS disorders. GRP78 antibodies may be a candidate target for promoting CNS transit of therapeutic antibodies for many CNS diseases.

【Purpose】To analyze the current situation in consideration of the patient’s age, gender, regional characteristics such as aging and depopulation, and make recommendations to improve the cancer screening examination rate.【Target and Method】From the data of Yamaguchi prefecture cancer registration 2008-2014, 25,044 people aged 31-80 of stomach, colon, and lung cancer were extracted. We analyzed the interrelationship among the degree of progress, the discovery route, and the discovery rate within the medical area.【Results】In all cancer nearly 80% cases were over 61 years. Cancer screening cases were often early. As the age group increased, the proportion discovered during follow-up of other diseases increased, the cancer screening percentage decreased. On the other hand, in cancer screening cases, the early percentage did not change even if the age increased. The medical examination rate within the medical care area increased by age.【Discussion and Conclusion】Change in the encourage system occurred at retirement might cause the cancer screening rate declines in elderly people. For elderly people doctor’s advice, active recommendation during retirement procedures and in community health, and announcing an attractive fact that over 80% of cancer screening are early even if you get older are necessary.

We encountered four female patients with jejunal gastrointestinal stromal tumor（GIST）between August 2006 and October 2018, of whom three were aged 75 years or older and one was in her 60s. Three patients had no clinical symptoms before surgery and one presented with anemia as a chief complaint. Preoperative contrast-enhanced computed tomography was performed before each surgery. Immunohistochemical examination of the surgical pathology specimens revealed that all cases were positive for KIT, thereby confirming the diagnosis of GIST. According to Fletcher’s classification, three cases were categorized as being low risk and one as intermediate risk. Therefore, no patient required postoperative adjuvant therapy. Three patients are currently alive and one died of intercurrent disease.