The PD-1, PD-L1 expression and CD3+ T cell infiltration in relation to outcome in advanced gastric signet-ring cell carcinoma, representing a potential biomarker for immunotherapy.

Jin, Shenying; Xu, Bo; Yu, Lan; Fu, Yao; Wu, Hongyan; Fan, Xiangshan; Liu, Baorui; Wei, Jia

doi:10.1200/jco.2017.35.15_suppl.e15609

Cited by 8 publications

(9 citation statements)

References 34 publications

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“…These ndings indicated that CD8 + T cells played a vital role in the anti-tumor effect of DDP. Previous studies showed that high levels of PD-1 + CD8 + T cells were associated with a poor prognosis for a range of cancers, including liver, pancreatic, and head and neck cancers [15][16][17][18]. In our study, further study showed that DDP also signi cantly reduced exhausted CD8 + T lymphocytes (PD-1 + CD8 + T cell) in the blood (Fig.…”

Section: Resultssupporting

confidence: 66%

Cisplatin Increased the Expression of PD-1 and PD-L1 by YAP1 in Hepatocellular Carcinoma

Hao

Guo

Peng

et al. 2021

Preprint

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Hepatocellular carcinoma (HCC) was one of the most malignant cancers in the world. Cisplatin (DDP) was one of the main chemotherapy drugs for HCC, but the mechanism of DDP treatment for HCC remains unclear. In this presentation, we found that DDP inhibited the growth of HCC cells and promoted the expression of PD-1 and its ligand PD-L1 in cancer cells. Meanwhile, flow cytometry analysis revealed that DDP enhanced PD-1-CD8+ T cells expression and decreased PD-1+CD8+ T cells expression. ELISA analysis suggested that DDP decreased TGF-β expression in vivo. Therefore, the study indicated that DDP enhanced PD-1 and PD-L1 expression and inhibited the growth of HCC.

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Section: Resultssupporting

confidence: 66%

Cisplatin Increased the Expression of PD-1 and PD-L1 by YAP1 in Hepatocellular Carcinoma

Hao

Guo

Peng

et al. 2021

Preprint

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“…Recently, 37 genes in tumorassociated macrophages that differed between breast cancer tissues and healthy controls were candidate loci for predicting survival [68]. Interestingly, Jin et al found that CD3 + T cells exhibit greater infiltration in PD-1 + tumors with MSI in Signet ring cell carcinoma, suggesting that there is a positive correlation between MSI and TILs [69]. Furthermore, EC with POLE mutations and MSI has more neoantigen and T cell infiltration, further demonstrating the association between these indicators and their value in predicting PD-1/PD-L1 blockade efficacy [44,70].…”

Section: Infiltration Of Immune Cells In the Tumor Microenvironment Imentioning

confidence: 99%

Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy

et al. 2020

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Immune checkpoint blockade targeting PD-1/PD-L1 has promising therapeutic efficacy in a variety of tumors, but resistance during treatment is a major issue. In this review, we describe the utility of PD-L1 expression levels, mutation burden, immune cell infiltration, and immune cell function for predicting the efficacy of PD-1/PD-L1 blockade therapy. Furthermore, we explore the mechanisms underlying immunotherapy resistance caused by PD-L1 expression on tumor cells, T cell dysfunction, and T cell exhaustion. Based on these mechanisms, we propose combination therapeutic strategies. We emphasize the importance of patient-specific treatment plans to reduce the economic burden and prolong the life of patients. The predictive indicators, resistance mechanisms, and combination therapies described in this review provide a basis for improved precision medicine.

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“…PD-1 expression is known to be associated with T cell exhaustion. In a general setting without immunotherapy, high PD-1 + CD8 + T cell levels are associated with a poor prognosis in a range of cancers, including liver cancer, pancreatic cancer, early breast cancer and head and neck cancers [40–45]. However, the notion that all PD-1 + immune cells are “exhausted” and, therefore, that they should be promoting pro-tumor immunity, may be an oversimplification.…”

Section: Introductionmentioning

confidence: 99%

“…Whether PD-1 is a marker of exhaustion, activation or both remains controversial, and PD-1 expression may only demonstrate that an immune cell has been recently stimulated, and is therefore antigen-experienced [47–51]. Furthermore, PD-1 expression on TILs, especially relative to tumor cell PD-L1 expression, is not a good predictive marker for PD-1/PD-L1 checkpoint blockade immunotherapy [40, 47, 52–55], and the function of these cells in many types of cancer, including TNBC, is not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of CD8 + PD-1+ immune infiltrates and PDCD1 gene expression in triple negative breast cancer

Yeong

Lim

Lee

et al. 2019

j. immunotherapy cancer

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The role of programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) in triple negative breast cancer (TNBC) remains to be fully understood. In this study, we investigated the role of PD-1 as a prognostic marker for TNBC in an Asian cohort (n = 269). Samples from patients with TNBC were labeled with antibodies against PD-L1 and PD-1, and subjected to NanoString assays to measure the expression of immune-related genes. Associations between disease-free survival (DFS), overall survival (OS) and biomarker expression were investigated. Multivariate analysis showed that tumors with high PD-1+ immune infiltrates harbored significantly increased DFS, and this increase was significant even after controlling for clinicopathological parameters (HR 0.95; P = 0.030). In addition, the density of cells expressing both CD8 and PD-1, but not the density of CD8−PD-1+ immune infiltrates, was associated with improved DFS. Notably, this prognostic significance was independent of clinicopathological parameters and the densities of total CD8+ cell (HR 0.43, P = 0.011). At the transcriptional level, high expression of PDCD1 within the tumor was significantly associated with improved DFS (HR 0.38; P = 0.027). In line with these findings, high expression of IFNG (HR 0.38; P = 0.001) and IFN signaling genes (HR 0.46; p = 0.027) was also associated with favorable DFS. Inclusion of PD-1 immune infiltrates and PDCD1 gene expression added significant prognostic value for DFS (ΔLRχ2 = 6.35; P = 0.041) and OS (ΔLRχ2 = 9.53; P = 0.008), beyond that provided by classical clinicopathological variables. Thus, PD-1 mRNA and protein expression status represent a promising, independent indicator of prognosis in TNBC.Electronic supplementary materialThe online version of this article (10.1186/s40425-019-0499-y) contains supplementary material, which is available to authorized users.

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The PD-1, PD-L1 expression and CD3+ T cell infiltration in relation to outcome in advanced gastric signet-ring cell carcinoma, representing a potential biomarker for immunotherapy.

Cited by 8 publications

References 34 publications

Cisplatin Increased the Expression of PD-1 and PD-L1 by YAP1 in Hepatocellular Carcinoma

Cisplatin Increased the Expression of PD-1 and PD-L1 by YAP1 in Hepatocellular Carcinoma

Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy

Prognostic value of CD8 + PD-1+ immune infiltrates and PDCD1 gene expression in triple negative breast cancer

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