PD-1 and PD-L1 Up-regulation Promotes T-cell Apoptosis in Gastric Adenocarcinoma

Chiu, Ying Ming; Tsai, Chung Lin; Kao, Jung Ta; Hsieh, Chin Tung; Shieh, Dong Chen; Lee, Yi Ju; Tsay, Gregory J.; Cheng, Ken Sheng; Wu, Yi

doi:10.21873/anticanres.12446

Cited by 25 publications

(18 citation statements)

References 23 publications

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“…It has been reported that anti-PD-1 antibody enhanced chemokine expression in tumors and T cell infiltration 24,40 . Others have also reported that anti-PD-1 antibody inhibited T cell apoptosis, and enhanced the proliferation of T cells 41 . According to these reports and our current data, we believe that anti-PD-1 antibody treatment induces the infiltration and accumulation of TAS0314-specific CTLs in the tumor microenvironment, which contributes to the synergistic antitumor effects.…”

Section: Discussionmentioning

confidence: 95%

TAS0314, a novel multi-epitope long peptide vaccine, showed synergistic antitumor immunity with PD-1/PD-L1 blockade in HLA-A*2402 mice

Tanaka

Wada

Goto

et al. 2020

Sci Rep

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Cancer peptide vaccines are a promising cancer immunotherapy that can induce cancer-specific cytotoxic T lymphocytes (CTLs) in tumors. However, recent clinical trials of cancer vaccines have revealed that the efficacy of the vaccines is limited. Targeting single antigens and vaccination with short peptides are partly the cause of the poor clinical outcomes. We synthesized a novel multi-epitope long peptide, TAS0314, which induced multiple epitope-specific CTLs in HLA knock-in mice. It also showed superior epitope-specific CTL induction and antitumor activity. We also established a combination treatment model of vaccination with PD-1/PD-L1 blockade in HLA-A*2402 knock-in mice, and it showed a synergistic antitumor effect with TAS0314. Thus, our data indicated that TAS0314 treatment, especially in combination with PD-1/PD-L1 blockade, is a promising therapeutic candidate for cancer immunotherapy.

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Section: Discussionmentioning

confidence: 95%

TAS0314, a novel multi-epitope long peptide vaccine, showed synergistic antitumor immunity with PD-1/PD-L1 blockade in HLA-A*2402 mice

Tanaka

Wada

Goto

et al. 2020

Sci Rep

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“…It is known that PD-L1 plays an important role in tumor development. PD-L1 has been speculated to play a major role in suppressing the immune system that allows immune escape of tumor cells [ 36 – 40 ]. Multiple researches show that PD-L1 is correlated with the progression of gastric cancer [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…Multiple researches show that PD-L1 is correlated with the progression of gastric cancer [ 40 ]. For example, PD-L1 is highly expressed in gastric cancer tissues and associated with a poor prognosis in patients with gastric cancer [ 36 , 41 ]. Overexpression of PD-L1 in peripheral blood may offer an immunological predictor of tumor progression and disease outcome in patients with gastric cancer [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

miR-502-5p affects gastric cancer progression by targeting PD-L1

et al. 2020

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Background: Studies have shown that miR-502-5p functions as a tumor suppressor and is associated with tumor growth and metastasis. This study intends to uncover the potential mechanism of miR-502-5p functioning as a tumor suppressor in gastric cancer. Methods: Expression levels of miR-502-5p and PD-L1 were measured by using qRT-PCR. Cell proliferation abilities were examined by EDU incorporation assay. Cell migration, invasion and cell cycle analysis of cells were determined by transwell assay, transwell-matrigel assay and flow cytometry, respectively. The relationship between miR-502-5p expression and the overall survival of xenograft tumor mice was statistically analyzed. Bioinformatics analysis and luciferase reporter assays were applied to analyze the relationship between miR-502-5p and CD40, STAT3 or PD-L1. Expressions of CD40, STAT3 and PD-L1 at protein level were detected by western blot. Results: The results showed that miR-502-5p was significantly downregulated in gastric cancer tumor tissues compared with adjacent normal tissues. Overexpression of miR-502-5p significantly attenuated the proliferation, migration/invasion and induced the G1 phase arrest of gastric cancer cells. Consistently, miR-502-5p suppressed tumor growth and metastasis in vivo. Mechanically, we demonstrated that miR-502-5p had inhibited the malignant behaviour of gastric cancer by down-regulating PD-L1 expression at transcriptional level and post-transcriptional levels. Conclusions: These findings suggest that miR-502-5p acts as a tumor suppressor in gastric cancer (GC). MiR-502-5p/ PD-L1 may be a novel therapeutic target in GC treatment.

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“…All data were analyzed using SPSS 15.0 for Windows 39 , 40 . Each experiment was performed in duplicate, and average values were used for quantification.…”

Section: Methodsmentioning

confidence: 99%

Isosteviol Derivative Inhibits Osteoclast Differentiation and Ameliorates Ovariectomy-Induced Osteoporosis

Tzeng

Huang

Tsai

et al. 2018

Sci Rep

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NC-8 (ent-16-oxobeyeran-19-N-methylureido) is an isosteviol-derived analogue with multiple biological effects, including anti-inflammation and anti-bacterial activities and inhibition of HBV viral surface antigen gene expression. In this study, we explored the effects of NC-8 on the formation of osteoclasts from RAW 264.7 cells. We found that NC-8 exerts the novel effect of inhibiting osteoclast-like cell formation. Our experiments showed that RANKL-induced ERK, p38, and JNK phosphorylation were inhibited by NC-8. An ovariectomy-induced osteoporosis animal model was used to examine the protective effects of oral treatment with NC-8. Serum analysis was used to examine markers of osteoblasts, osteoclasts, and renal and hepatic function in rats. Micro CT scanning and histological analysis were used to measure bone loss in ovariectomized rats. Oral administration of NC-8 effectively decreased excess bone resorption and significantly antagonized trabecular bone loss in ovariectomized rats. Serum analysis of C-terminal telopeptide of type-I collagen, an osteoclast marker, also showed that NC-8 administration inhibited excess bone resorption. Furthermore, serum analysis showed that renal and liver function were not affected by these doses of NC-8 during long-term treatment. Our results demonstrate that NC-8 inhibits osteoclast differentiation and effectively ameliorates ovariectomy-induced osteoporosis.

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PD-1 and PD-L1 Up-regulation Promotes T-cell Apoptosis in Gastric Adenocarcinoma

Abstract: This study provides evidence for a new therapeutic target in gastric adenocarcinoma patients.

Cited by 25 publications

References 23 publications

TAS0314, a novel multi-epitope long peptide vaccine, showed synergistic antitumor immunity with PD-1/PD-L1 blockade in HLA-A*2402 mice

TAS0314, a novel multi-epitope long peptide vaccine, showed synergistic antitumor immunity with PD-1/PD-L1 blockade in HLA-A*2402 mice

miR-502-5p affects gastric cancer progression by targeting PD-L1

Isosteviol Derivative Inhibits Osteoclast Differentiation and Ameliorates Ovariectomy-Induced Osteoporosis

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