YH29407 with anti-PD-1 ameliorates anti-tumor effects via increased T cell functionality and antigen presenting machinery in the tumor microenvironment

Among cancer cells, indoleamine 2, 3-dioxygenase1 (IDO1) activity has been implicated in improving the proliferation and growth of cancer cells and suppressing immune cell activity. IDO1 is also responsible for the catabolism of tryptophan to kynurenine. Depletion of tryptophan and an increase in kynurenine exert important immunosuppressive functions by activating regulatory T cells and suppressing CD8+ T and natural killer (NK) cells. In this study, we compared the anti-tumor effects of YH29407, the best-in-class IDO1 inhibitor with improved pharmacodynamics and pharmacokinetics, with first and second-generation IDO1 inhibitors (epacadostat and BMS-986205, respectively). YH29407 treatment alone and anti-PD-1 (aPD-1) combination treatment induced significant tumor suppression compared with competing drugs. In particular, combination treatment showed the best anti-tumor effects, with most tumors reduced and complete responses. Our observations suggest that improved anti-tumor effects were caused by an increase in T cell infiltration and activity after YH29407 treatment. Notably, an immune depletion assay confirmed that YH29407 is closely related to CD8+ T cells. RNA-seq results showed that treatment with YH29407 increased the expression of genes involved in T cell function and antigen presentation in tumors expressing ZAP70, LCK, NFATC2, B2M, and MYD88 genes. Our results suggest that an IDO1 inhibitor, YH29407, has enhanced PK/PD compared to previous IDO1 inhibitors by causing a change in the population of CD8+ T cells including infiltrating T cells into the tumor. Ultimately, YH29407 overcame the limitations of the competing drugs and displayed potential as an immunotherapy strategy in combination with aPD-1

Flora of Jeokgeunsan Mountain in the Civilian Control Zone, Gangwon-do, South Korea

The flora of Jeokgeunsan Mountain forest genetic resources protection zone was identified and the major flora distribution examined. From May 2011 to September 2012, the flora was made up of taxonomic groups including 84 families, 283 genera, 432 species, four subspecies, 59 varieties, and six forma. Eleven families and 16 taxonomic groups were endemic plants to Korea, and 13 taxonomic groups were rare flora of Korea designated by the National Forest Service. Eight families and 24 taxonomic groups for naturalized plants were confirmed and the naturalization rate was 4.8%. Out of 501 taxonomic groups, 404 were resource plants of which 208 (41.5%) were edible plants, 152 (30.3%) were medicinal plants, 199 (39.7%) were herbaceous plants, and 55 (11.0%) were ornamental plants

Species composition, diversity, and distribution of the genus Ulva along the coast of Jeju Island, Korea based on molecular phylogenetic analysis.

Species diversity in the genus Ulva remains understudied worldwide. Using molecular analyses we investigated the species composition, diversity, distribution, and relative frequencies of the genus Ulva along the entire coast of Jeju Island, off the southern tip of Korea. Species identification was performed for 215 samples collected from 23 sites, based on comprehensive phylogenetic and model-based species delimitation analyses using the sequences of two molecular markers, chloroplast elongation factor Tu (tufA) and nuclear rDNA internal transcribed spacer (ITS). We identified 193 specimens as nine Ulva species, 14 specimens as Blidingia spp., and eight samples undetermined, based on the combined analysis of tufA and ITS phylogenies. Two model-based approaches generally supported nine groups of Ulva species. Previously documented species complex, such as U. ohnoi-U. spinulosa and U. procera-U. linza showed discordant relationships between the two phylogenies. The occurrence of U. torta on Jeju Island was first observed, despite its existence on the mainland previously reported. Ulva australis [16 of 23 sites; 34.4% (relative frequency)], U. ohnoi (16; 21.9%), and U. procera (11; 14%) were found to be the predominant species. Our study highlights that molecular analysis is critical for species delimitation in the genus Ulva and provides fundamental information for an understanding of green-tide assemblages on the "biological hotspot" coastal ecosystem, Jeju Island in Korea. This study will also help to monitor and manage local green tides at the areas that are currently encountering rapid climate changes

Under-diagnosis of vector-borne diseases among individuals suspected of having Scrub Typhus in South Korea.

Due to environmental and ecological changes and suitable habitats, the occurrence of vector-borne diseases is increasing. We investigated the seroprevalence of four major vector-borne pathogens in human patients with febrile illness who were clinically suspected of having Scrub Typhus (ST) caused by Orientia tsutsugamushi. A total of 187 samples (182 patient whole blood and sera samples, including 5 follow-up) were collected. Antibodies to Anaplasma phagocytophilum, Ehrlichia chaffeensis, Borrelia burgdorferi, and Bartonella henselae were tested by using indirect immunofluorescence assays. Molecular diagnoses were performed using real-time PCR. Of the 182 cases, 37 (20.3%) cases were designated as confirmed cases of ST, and the remaining 145 (79.7%) cases as other febrile diseases (OFDs). The seroprevalence of A. phagocytophilum, E. chaffeensis, B. burgdorferi, and B. henselae was 51.4% (19/37), 10.8% (4/37), 86.5% (32/37), and 10.8% (4/37) among the ST group, and 42.8% (62/145), 10.4% (19/145), 57.7% (105/145), and 15.9% (29/145) among the OFD group, respectively. There were no significant differences in the seroprevalence between the ST and the OFD groups. Considering the co-occurrence, 89.0% (162/182) had at least one antibody to tick-borne pathogens, 37.0% (60/162) were positive for two pathogens, 17.3% (28/162) for three pathogens, and 6.2% (10/162) for four pathogens. In real-time PCR, O. tsutsugamushi was positive in 16 cases [15 (40.5%) in ST group and 1 (2.2%) in OFD group], and the four other pathogens were negative in all cases except one confirmed as anaplasmosis. In evaluating the five follow-up samples, the appearance of new antibodies or an increase in the pre-existing antibody titers was detected. Our data highlighted that acute febrile illness and manifestations suggestive of a vector-borne infection must be recognized and further considered for coinfections in clinical practice and the laboratory

Histomorphological and Immunophenotypic Features of Pill-Induced Esophagitis

<div><p>The aim of this study was to investigate histomorphological and immunophenotypic features in pill-induced esophagitis. We comparatively evaluated the histomorphological, immunophenotypic features of pill-induced esophagitis vs. reflux esophagitis, as well as clinical information and endoscopic findings. Fifty-two tissue pieces from 22 cases of pill-induced esophagitis, 46 pieces from 20 reflux esophagitis, and 16 pieces from 14 control samples were subjected to immunohistochemistry for inflammatory infiltrates (CD3 for T lymphocyte, CD20 for B lymphocyte, CD56 for NK cell, CD68 for macrophage, CD117 for mast cell) and eosinophil chemotaxis-associated proteins (Erk, leptin, leptin receptor, pSTAT3, phospho-mTOR). As a result, Histomorphology showed that a diffuse pattern of dilated intercellular spaces was more frequently observed in pill-induced esophagitis, while reactive atypia and subepithelial papillary elongation were more often found in reflux esophagitis (<i>P</i> < 0.05, respectively). Interestingly, intraepithelial eosinophilic microabscess, intraepithelial pustule and diffuse pattern of dilated intercellular spaces were observed in 14% (3 cases), 9% (2 cases) and 32% (7 cases) of pill-induced esophagitis, respectively, but in no cases of reflux esophagitis. Regarding intraepithelial inflammatory infiltrates in pill-induced esophagitis, T lymphocytes were the most common cells, followed by eosinophil; 11 and 7 in one x400 power field, respectively. Intraepithelial pSTAT3-positive pattern was more frequently observed in pill-induced esophagitis than in reflux esophagitis, at 45% (10 cases) versus 10% (2 cases), respectively (<i>P</i> < 0.05). Considering the distal esophageal lesion only, intraepithelial pustule, diffuse dilated intercellular spaces and stromal macrophages were more frequently found in distal pill-induced esophagitis, whereas reactive atypia and intraepithelial mast cells in reflux esophagitis (<i>P</i> < 0.05, respectively). In conclusion, diffuse dilated intercellular spaces, intraepithelial eosinophil microabscess, pustule, T lymphocytes, eosinophils, and pSTAT3 positivity can be added to histopathological features of pill-induced esophagitis, other than non-specific ulcer. Besides, distal pill-induced esophagitis may be histopathologically differentiated from reflux esophagitis.</p></div

Clinical features of pill-induced esophagitis and reflux esophagitis groups.

<p>^a<i>P</i> value between pill-induced esophagitis and reflux esophagitis groups.</p><p>^bNS, not significant.</p><p>Clinical features of pill-induced esophagitis and reflux esophagitis groups.</p