Impressive response to immunotherapy in a metastatic gastric cancer patient: could somatic copy number alterations help patient selection?

Fernandes, Gustavo dos Santos; Girardi, Daniel M.; Faria, Luiza Dib Batista Bugiato; Bernardes, João Paulo Giacomini; Coudry, Renata de Almeida

doi:10.1186/s40425-017-0291-9

Cited by 5 publications

(3 citation statements)

References 22 publications

(20 reference statements)

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“…despite a number of achievements in chemotherapy and alternative therapeutic agents, there has been no major improvement in the overall survival in patients with gastric cancer over the past decade (22). immunotherapy is a relatively recent strategy in gastric cancer therapy (23)(24)(25). However, the impact of immunotherapy in gastric cancer is unsatisfactory.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑140 suppresses Helicobacter pylori‑positive gastric cancer growth by enhancing the antitumor immune response

Zhao

Liu

et al. 2019

Mol Med Report

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immune checkpoint blockade is a promising therapeutic strategy against various human malignancies. Micrornas (mirnas/mirs) regulate gene expression, by repressing mrna translation or promoting its degradation. The aim of the current study was to investigate the role and molecular mechanisms of mir-140 in Helicobacter pylori (Hp)-associated gastric cancer, and to examine its relationship with immune function in gastric cancer. Gastritis tissue samples from gastritis patients, and gastric cancer tissue samples from gastric cancer patients were collected for mir-140 expression detection. mir-140 expression was detected using reverse transcription-quantitative polymerase chain reaction, and protein expression was measured by western blotting. TargetScan and dual luciferase reporter assays were used to reveal the association between mir-140 and programmed cell death-ligand 1 (Pd-l1). BGc823 cell proliferation was detected by MTT assays. Ex vivo immune analysis by flow cytometry and ELISA were used to analyze immune function. it was demonstrated that mir-140 expression was significantly reduced in Hp-positive gastric cancer. PD-L1 was confirmed as a direct target of miR-140 in gastric cancer cells. In addition, PD-L1 expression was significantly increased in Hp-positive gastric cancer. overexpression of miR-140 significantly suppressed gastric cancer cell proliferation through regulating Pd-l1 expression. In vivo experiments also revealed that mir-140 markedly repressed tumor growth in the c57Bl/6 mice. Furthermore, it was determined that the tumor-suppressive role of mir-140 in gastric cancer was associated with increased cytotoxic cd8 + T cell and reduced myeloid-derived suppressive and regulatory T cell infiltration. miR-140 significantly prevented mammalian target of rapamycin signaling in gastric cancer cells. notably, these mir-140 overexpression-induced alterations were inhibited by PD-L1 plasmid. These findings indicated that miR-140 exerted an anti-gastric cancer effect by targeting immune checkpoint molecule Pd-l1. Thus, mir-140 may be a promising and novel immunotherapeutic target for gastric cancer treatment.

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Section: Introductionmentioning

confidence: 99%

MicroRNA‑140 suppresses Helicobacter pylori‑positive gastric cancer growth by enhancing the antitumor immune response

Zhao

Liu

et al. 2019

Mol Med Report

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“…However, the selection of patients based solely on the PD-L1 expression and/or MSI profiles may exclude those who might benefit from immunotherapy. 14 Despite our patient’s tumor being PD-L1-negative with pMMR, SHR-1701 in combination with famitinib yielded a long-lasting positive outcome. Beyond ICIs, the roles of TGF-β and famitinib cannot be overlooked.…”

Section: Discussionmentioning

confidence: 73%

Long-lasting complete response to SHR-1701 plus famitinib in refractory advanced gallbladder cancer: A case report

Yi,

Zhu,

Xie

et al. 2023

Human Vaccines & Immunotherapeutics

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Biliary tract cancer (BTC) is an aggressive malignancy with few options for advanced-stage treatment. The combination of PD-1/PD-L1 inhibitors with famitinib, a receptor tyrosine kinase (RTK) inhibitor, has demonstrated improved clinical outcomes in several clinical trials. We herein reported a case of a gallbladder cancer (GBC) patient with liver metastases, previously resistant to traditional chemotherapy. Remarkably, the patient achieved a complete response (CR) with a long-lasting survival benefit exceeding 3 years. This was achieved using a novel regimen combining SHR-1701, an anti-PD-L1/TGF-βR fusion protein, and famitinib, even though the patient had proficient mismatch repair (pMMR) and tested negative for PD-L1. Adverse events were limited and manageable. This is the first report of such a treatment regimen being applied in a clinical setting, suggesting that the SHR-1701 and famitinib combination may be a promising immunotherapeutic approach for patients with refractory advanced GBC.

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“…Gastric cancer (GC) is the fifth most common malignant neoplasm in humans worldwide and the third leading cause of death among patients with cancer [ 1 ]. The early-stage GC patients were treated with various significant therapies.…”

Section: Introductionmentioning

confidence: 99%

miR-504 Promoted Gastric Cancer Cell Proliferation and Inhibited Cell Apoptosis by Targeting RBM4

Zhang

Yong

et al. 2021

Journal of Immunology Research

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Background. The purpose of this study was to explore the role and underlying mechanism of miR-504 and RBM4 in gastric cancer. Methods. The qRT-PCR or Western blot was performed to determine the expressions of miR-504 and RBM4 in the gastric cancer tissues and normal tissues. Human SGC-7901 cells were transfected with miR-504 mimic/inhibitor or pcDNA-RBM4. Cell proliferation and cell apoptosis were assessed by colony formation assay and flow cytometry, respectively. Luciferase reporter gene assays were used to investigate interactions between miR-504 and RBM4 in SGC-7901 cells. Results. The relative expression of miR-504 was significantly upregulated in the gastric cancer group ( n = 25 ) than in the paired normal group ( n = 25 ), but the relative RBM4 expression was remarkably downregulated in the gastric tumor group, compared with the normal group. Additionally, miR-504 overexpression increased the viability of gastric cancer cells. Moreover, RBM4 is a functional target of miR-504 in gastric cancer cells. miR-504 was further confirmed to promote SGC-7901 cell proliferation and inhibit cell apoptosis by downregulation RBM4 in vitro. Conclusions. miR-504 promotes gastric cancer cell proliferation and inhibits cell apoptosis by targeting RBM4, and this provides a potential diagnostic biomarker and treatment for patients with gastric cancer.

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Impressive response to immunotherapy in a metastatic gastric cancer patient: could somatic copy number alterations help patient selection?

Cited by 5 publications

References 22 publications

MicroRNA‑140 suppresses Helicobacter pylori‑positive gastric cancer growth by enhancing the antitumor immune response

MicroRNA‑140 suppresses Helicobacter pylori‑positive gastric cancer growth by enhancing the antitumor immune response

Long-lasting complete response to SHR-1701 plus famitinib in refractory advanced gallbladder cancer: A case report

miR-504 Promoted Gastric Cancer Cell Proliferation and Inhibited Cell Apoptosis by Targeting RBM4

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