Correlation between infiltration of FOXP3+ regulatory T cells and expression of B7-H1 in the tumor tissues of gastric cancer

Hou, Jinlin; Zhong, Yu; Xiang, Rengyun; Li, Chuqiang; Wang, Lin; Chen, Shufen; Li, Qingyun; Chen, Mei; Wang, Linyun

doi:10.1016/j.yexmp.2014.03.005

Cited by 130 publications

(95 citation statements)

References 30 publications

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“…Despite the marked heterogeneity of the published literature analyzing TILs in various tumor types [18,19], there is now a general consensus that TILs are a favorable feature, particularly in locally advanced, radically resected tumors. Nonetheless, data in metastatic patients were lacking-that is, data correlating TILs with response and PFS in this setting.…”

Section: Discussionmentioning

confidence: 99%

Mismatch repair deficiency may affect clinical outcome through immune response activation in metastatic gastric cancer patients receiving first-line chemotherapy

et al. 2016

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Introduction The microsatellite-instable gastric cancer subtype, because of its supposed high antigenic potential, is a promising candidate for immunotherapy. We analyzed if the presence of a defective mismatch repair (MMR) system is associated with other markers of immune response and their relationship with outcome in advanced gastric cancer patients. Methods We analyzed the relationship between clinical outcome and MMR status, the presence of tumor-infiltrating lymphocytes (TIL), lymphocytosis, and neutrophil-tolymphocyte ratio (NLR) in metastatic gastric cancer patients treated with a chemotherapy doublet in the firstline setting. Other stratification factors were sex, age, Eastern Cooperative Oncology Group performance status, adjuvant/neoadjuvant chemotherapy, metastatic sites, and histotype. Results One hundred three patients were eligible for analysis. Defective MMR was found in 15 patients (14 %), TILs were found in 18 patients (17 %), lymphocytosis was found in 24 patients (23 %), and high NLR was found in 75 patients (72 %). Significant correlations were found between defective MMR and TIL positivity (p = 0.0004), between defective MMR and lymphocytosis (p = 0.0062), between defective MMR and low NLR (p = 0.000069), and between TIL positivity and lymphocytosis (p = 0.000147). All factors had a statistically significant impact on overall survival, although on multivariate analysis only defective MMR (p = 0.0001) and TIL positivity (p = 0.0192) maintained their independent prognostic role. Similar results were observed for progression-free survival, with defective MMR (p = 0.0001) and TIL positivity (p = 0.0195) maintaining their prognostic role on multivariate analysis. Conclusions Our analysis confirms the favorable prognosis of metastatic gastric cancer patients with a defective MMR system and suggests that expression of TILs might also be linked to better outcome. Because of the correlation between defective MMR status and measures of immune system activity, this group of patients would be the best candidates for novel immunotherapy-based therapies.

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Section: Discussionmentioning

confidence: 99%

Mismatch repair deficiency may affect clinical outcome through immune response activation in metastatic gastric cancer patients receiving first-line chemotherapy

et al. 2016

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“…[32][33][34][35][36] Importantly, emerging evidence demonstrated that EBV is present in a considerable amount of tumor cells of gastric cancer patients worldwide. Studies confirmed that EBV-positive gastric cancer cell line (AGS-EBV) was resistant to the chemotherapy drugs docetaxel and 5-fluorouracil as compared with EBV-negative cells (AGS).…”

Section: E1249558-10mentioning

confidence: 99%

CRISPR-Cas9-mediated disruption of PD-1 on human T cells for adoptive cellular therapies of EBV positive gastric cancer

Zou

Chen

et al. 2016

OncoImmunology

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The successful use of immune cell checkpoint inhibitors PD-1 and PD-L1, over the past 5 y has raised the concern of using immunotherapy to treat various cancers. Epstein-Barr virus-associated gastric cancer (EBVaGC) exhibits high infiltration of lymphocytes and high amplification of immune-related genes including PD-L1 as distinguished from Epstein-Barr virus-non-associated gastric cancer (EBVnGC). Here, we presume that this PD-1/PD-L1 pathway may hinder the efficacy of adoptive T cell therapy toward EBVaGC. These studies reveal possibility of generating PD-1-disrupted CTL by CRISPR-Cas9 system and demonstrate enhanced immune response of these PD-1-disrupted CTLs to the EBV-LMP2A antigen and superior cytotoxicity to the EBV-positive gastric cancer cell. In addition, when combined with low-dose radiotherapy, these PD-1-disrupted CTLs mediated an impressive antitumor effect in a xenograft mouse model of EBVaGC. Taken together, these studies illustrate PD-1/PD-L1-mediated immune tolerance of EBVaGC and provide a new strategy for targeting immune checkpoints to break the tolerance for the T cell-based adoptive therapy.

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“…Similarly, PD-L1 overexpression was found in 40% of cases of advanced GC from the phase Ib KEYNOTE-012 trial data [11]. Another Chinese study (n = 111) reported PD-L1 positivity in 63% of GC resection specimens [23].…”

Section: Pd-1/pd-l1 Expression and Patient Outcomementioning

confidence: 89%

“…Additionally, PD-L1 upregulation has been detected in gastrointestinal malignancies, such as pancreatic, colorectal, and GC, correlating with poor prognosis [27,28]. Likewise, high PD-L1 expression in GC was associated with nodal metastases, advanced stage, and poor outcome [22,23]. Recently, a small cohort study showed that resected GC patients with a higher CD8+ T-cell density have a higher PD-L1 expression and worse clinical outcome [29].…”

Section: Pd-1/pd-l1 Expression and Patient Outcomementioning

confidence: 99%

Anti-programmed death ligand 1 (PD-L1) inhibitors in metastatic gastric cancer

Cho

Lee

2017

Precis Future Med

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Metastatic gastric cancer (GC) with limited therapeutic options has a poor prognosis, and therefore, major therapeutic advances are needed. Comprehensive genomic characterization has improved understanding of GC but a great majority of genomic profiling has not been effectively translated to the clinical benefit yet. The introduction of immunotherapy with anti-programmed death ligand 1 (PD-L1) antibody such as pembrolizumab or nivolumab resulted in a rapid paradigm shift in the field of medical oncology and their clinical indication has been expanding in the past few years. Now, the era of immunotherapy in metastatic GC has arrived with recent trial results in survival benefit from anti-PD-L1 antibody. Herein, we review the mechanisms of immunotherapy, clinical trials that have been conducted or are in progress, and the potential for PD-L1 as a predictive biomarker for GC.

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Correlation between infiltration of FOXP3+ regulatory T cells and expression of B7-H1 in the tumor tissues of gastric cancer

Cited by 130 publications

References 30 publications

Mismatch repair deficiency may affect clinical outcome through immune response activation in metastatic gastric cancer patients receiving first-line chemotherapy

Mismatch repair deficiency may affect clinical outcome through immune response activation in metastatic gastric cancer patients receiving first-line chemotherapy

CRISPR-Cas9-mediated disruption of PD-1 on human T cells for adoptive cellular therapies of EBV positive gastric cancer

Anti-programmed death ligand 1 (PD-L1) inhibitors in metastatic gastric cancer

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