Immunotherapy targeting programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1) represents promising treatments for human cancers. Our previous studies demonstrated PD-L1 overexpression in some canine cancers, and suggested the therapeutic potential of a canine chimeric anti-PD-L1 monoclonal antibody (c4G12). However, such evidence is scarce, limiting the clinical application in dogs. In the present report, canine PD-L1 expression was assessed in various cancer types, using a new anti-PD-L1 mAb, 6C11-3A11, and the safety and efficacy of c4G12 were explored in 29 dogs with pulmonary metastatic oral malignant melanoma (OMM). PD-L1 expression was detected in most canine malignant cancers including OMM, and survival was significantly longer in the c4G12 treatment group (median 143 days) when compared to a historical control group (n = 15, median 54 days). In dogs with measurable disease (n = 13), one dog (7.7%) experienced a complete response. Treatment-related adverse events of any grade were observed in 15 dogs (51.7%). Here we show that PD-L1 is a promising target for cancer immunotherapy in dogs, and dogs could be a useful large animal model for human cancer research.

Bovine leukemia virus (BLV) infection is a chronic viral infection of cattle and endemic in many countries, including Japan. Our previous study demonstrated that PGE 2 , a product of cyclooxygenase (COX) 2, suppresses Th1 responses in cattle and contributes to the progression of Johne disease, a chronic bacterial infection in cattle. However, little information is available on the association of PGE 2 with chronic viral infection. Thus, we analyzed the changes in plasma PGE 2 concentration during BLV infection and its effects on proviral load, viral gene transcription, Th1 responses, and disease progression. Both COX2 expression by PBMCs and plasma PGE 2 concentration were higher in the infected cattle compared with uninfected cattle, and plasma PGE 2 concentration was positively correlated with the proviral load. BLV Ag exposure also directly enhanced PGE 2 production by PBMCs. Transcription of BLV genes was activated via PGE 2 receptors EP2 and EP4, further suggesting that PGE 2 contributes to disease progression. In contrast, inhibition of PGE 2 production using a COX-2 inhibitor activated BLV-specific Th1 responses in vitro, as evidenced by enhanced T cell proliferation and Th1 cytokine production, and reduced BLV proviral load in vivo. Combined treatment with the COX-2 inhibitor meloxicam and anti-programmed death-ligand 1 Ab significantly reduced the BLV proviral load, suggesting a potential as a novel control method against BLV infection. Further studies using a larger number of animals are required to support the efficacy of this treatment for clinical application.

The surface energy flux balance and total evapotranspiration were estimated using the eddy correlation, and bandpass covariance technique over a tropical monsoon environment within the framework of GEWEX (Global Energy and Water cycle Experiment) Asian Monsoon Experiment (GAME). The aim of this present study is to obtain information on the seasonal variation of heat and water vapor exchanges between the atmosphere and terrestrial land cover (complex area) in tropical monsoon environment.The result indicated the daily integrated values of net radiation, sensible heat, latent heat and ground heat flux during the observation period from July 1998 to February 1999 were 10.76 MJ m À2 , 2.32 MJ m À2 , 5.18 MJ m À2 and 0.03 MJ m À2 , respectively. Sensible and latent heat fluxes were the dominant energy partitioning components throughout the year. The seasonal difference in surface fluxes between wet and dry seasons was seen, and the latent heat flux was dominant in the monsoon, corresponding with the increase of specific humidity after frequent precipitation. Whereas the sensible heat flux increased as the surface temperature increased in the absence of rainfall during the dry season. However, the closure of energy balance remained unresolved as with the foregoing experimental studies. The estimated amount to evapotranspiration was 526 mm versus 641 mm of actual precipitation, and accounted for about 80% of the precipitation during this period.