Current status of immune checkpoint inhibitors for gastric cancer

Kono, Koji; Nakajima, Shotaro; Mimura, Kosaku

doi:10.1007/s10120-020-01090-4

Cited by 166 publications

(141 citation statements)

References 88 publications

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“…Many studies including ours reveal that expressions of CXCL 9, 10, 11 are related to the efficacy of PD-L1/PD-1 blockades in GC. 3,37 Meanwhile, all receptors of CXCL 9, 10, 11 are CXCR3 and CXCL9, 10, 11/CXCR3 axis leads migration of immune cells to their focal sites. 38 The researches show that CXCL9, 10, 11/CXCR3 axis involves directing the migration of CD8 + T cells to the tumor site and inducing their potentiation and proliferation there.…”

Section: Discussionmentioning

confidence: 99%

“…For localized gastric cancer, curative resection is a standard and preferred treatment, but the recurrence rate remains high, with a five-year survival of less than 25% and median overall survival (OS) of 7 to 10 months after diagnosis. 2,3 For unresectable or metastatic advanced GC, cytotoxic chemotherapy is mostly used. However, cytotoxic chemotherapy is nonspecific and has serious adverse reactions, the outcomes being usually poor.…”

Section: Introductionmentioning

confidence: 99%

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M1-like TAMs are required for the efficacy of PD-L1/PD-1 blockades in gastric cancer

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

M1-like TAMs are required for the efficacy of PD-L1/PD-1 blockades in gastric cancer

et al. 2020

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“…According to a study of The Cancer Genome Atlas (TCGA), as well as recent clinical trials, EBV and MSI GC subgroups may bene t from therapy with PD-1/PD-L1 antibodies [10,11]. Furthermore, PD-1/PD-L1 inhibitors appear to enhance antitumor activity in patients with advanced GC [12][13][14][15]. However, the frequency and prognostic value of PD-L1 expression in GC remain controversial.…”

Section: Introductionmentioning

confidence: 99%

Clinicopathological features of Epstein-Barr virus infection, microsatellite instability, tumor mutation burden and PD-L1 status in Chinese patients with gastric cancer

Zhang

Li³

2020

Preprint

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Objectives: Gastric cancer (GC) is the 4th most common type of cancer worldwide. Different GC subtypes exhibit unique molecular features that may potentially guide therapeutic decisions. The aim of the present study was to investigate Epstein-Barr virus (EBV) infection, microsatellite instability (MSI) status, the expression of programmed death-ligand 1 (PD-L1) and gene mutations in patients with surgically-treated GC. Methods: The data of 2,504 GC patients, who underwent potentially curative gastrectomy with lymphadenectomy at Peking University Cancer Hospital between 2013 and 2018, were reviewed from a prospectively collected medical database. We also analyzed the clinicopathological factors associated with the immunohistochemistry (IHC) profiles of these patients, and genetic alterations were analyzed using next generation sequencing (NGS). Results: Mismatch repair-deficient (d-MMR) GC patients were found to have a higher probability of expressing PD-L1 (p<0.001, PD-L1 cutoff value = 1%). In addition, 4 and 6.9% of the 2,504 gastric cancer patients were EBV-positive and d-MMR, respectively. The number of MLH1/PMS2-negative cases was 126 (6%), and the number of MSH2/MSH6-negative cases was 14 (0.9%). d-MMR status was associated with a diffuse/mixed group (p<0.05), but not with tumor differentiation. Furthermore, MSI and d-MMR GC status (detected by NGS and IHC, respectively) were consistently high, and the rate of MSI was higher in patients with d-MMR GC. A number of genes associated with DNA damage repair were detected in GC patients with MSI, including POLE, ETV6, BRCA and RNF43. In patients with a high tumor mutation burden, the most significantly mutated genes were LRP1B (79.07%), ARID1A (74.42%), RNF43 (69.77%), ZFHX3 (65.12%), TP53 (58.14%), GANS (51.16%), BRCA2 (51.16%), PIK3CA (51.16%), NOTCH1 (51.16%), SMARCA4 (48.84%), ATR (46.51%), POLE (41.86%) and ATM (39.53%). Conclusions: Using IHC and NGS, MSI status, protein expression, TMB and genetic alterations were identified in patients with GC, which provides a theoretical basis for the future clinical treatment of GC.

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“…According to The Cancer Genome Atlas (TCGA) study and recent trials, EBV and MSI GC subgroups may bene t from therapy with PD-1/PD-L1 antibodies [10,11].PD-1/PD-L1 inhibitors appear to improve the antitumor activity in advanced gastric cancer patients [12][13][14][15]. However, the frequency and prognostic value of PD-L1 expression in GC remain controversial.…”

Section: Introductionmentioning

confidence: 99%

Clinic-pathological Features of Epstein-barr Virus Infection, Microsatellite Instability, Tumor Mutation Burden and PD-L1 Status in 2504 Chinese Gastric Cancer Patients

Zhang

2020

Preprint

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Objectives: Gastric cancer is the 4th most common cancer worldwide. Different subtype showed unique molecular features that could potentially guide therapeutic decisions. The aim of this study was to investigate the Epstein-Barr virus infection, microsatellite instability status, PD-L1 expression and gene mutation in surgically treated gastric cancer patients. Methods: We reviewed all GC patients who underwent potentially curative gastroectomy with lymphadenectomy at Peking University Cancer Hospital between 2013 and 2018 from a prospective collected medical database. We analyzed the clinic-pathological factors associated with immunohistochemistry profiles. We also analyzed gene changes through next-generation sequencing. Results: d-MMR gastric cancer patients are more likely to expression programmed death-ligand 1 (p<0.001, programmed death-ligand 1 cut off value 1%). EBV-positive and d-MMR patients were identified in 4% and 7.5% of the 2504 gastric cancer patients, respectively. The MLH1/PMS2 negative case number was 126. The MSH2/MSH6 negative case number was 14. d-MMR status was related to diffuse/mixed group (p<0.05), but not related to tumor differentiation. In our study, the microsatellite instability results detected by next generation sequencing and d-MMR gastric cancer results detected by immunohistochemistry were in high consistency. d-MMR gastric cancer patients had more microsatellite instability core. Many pathogenic genes were detected in microsatellite instability gastric cancer patients, such as POLE, ETV6, TP53, BRCA, RNF43 and other genes. Conclusion: Through immunohistochemistry and next generation sequencing, we got MSI status, protein expression, TMB and gene changes of GC, which provided a theoretical basis for future G clinical treatment.

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Current status of immune checkpoint inhibitors for gastric cancer

Cited by 166 publications

References 88 publications

M1-like TAMs are required for the efficacy of PD-L1/PD-1 blockades in gastric cancer

M1-like TAMs are required for the efficacy of PD-L1/PD-1 blockades in gastric cancer

Clinicopathological features of Epstein-Barr virus infection, microsatellite instability, tumor mutation burden and PD-L1 status in Chinese patients with gastric cancer

Clinic-pathological Features of Epstein-barr Virus Infection, Microsatellite Instability, Tumor Mutation Burden and PD-L1 Status in 2504 Chinese Gastric Cancer Patients

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