PD-1 and PD-L1 co-expression predicts favorable prognosis in gastric cancer

Wu, Yanhua; Cao, Donghui; Qu, Limei; Cao, Xueyuan; Jia, Zhifang; Zhao, Tong; Wang, Quan; Jiang, Jing

doi:10.18632/oncotarget.19318

Cited by 61 publications

(67 citation statements)

References 54 publications

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“…demonstrated PD-1 to be an independent prognostic factor for both OS and disease-free survival in patients with MSS tumours. 17 Moreover, PD-1 expression has been demonstrated to carry an independent favourable impact in gastric, 47 ovarian, 48 and head and neck cancer, 49 among others. Further studies are warranted to elucidate the prognostic impact of PD-1 expression in CRC, particularly regarding PTL.…”

Section: Discussionmentioning

confidence: 99%

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis

et al. 2018

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Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 has been demonstrated to confer a prognostic value in colorectal cancer (CRC), but no studies have investigated whether this association differs according to tumour location. In this study, immunohistochemical expression of PD-1 and PD-L1 was analysed in tissue microarrays with primary tumours from 557 incident CRC cases from a prospective population-based cohort. Univariable and multivariable Cox regression analyses, adjusted for age, sex, TNM stage, differentiation grade and vascular invasion, were applied to determine the impact of biomarker expression on 5-year overall survival (OS), in the entire cohort and in subgroup analysis of right colon, left colon, and rectum. High PD-L1 expression on tumour-infiltrating immune cells was an independent factor of a prolonged OS in the entire cohort (hazard ratio [HR] = 0.49; 95% confidence interval [CI] CI 0.35 – 0.68), and in tumours of the right colon (HR = 0.43; 95% CI 0.25 – 0.74) and the left colon (HR = 0.28; 95% CI 0.13 – 0.61), but not in rectal cancer. Tumour-specific PD-L1-expression was not prognostic, neither in the full cohort nor according to tumour location. High immune cell-specific PD-1 expression was associated with a prolonged OS in the entire cohort and in tumours of the right colon, but not in the left colon or rectum, and only in univariable analysis. In conclusion, these results demonstrate that immune cell-specific PD-L1 and PD-1 expression is prognostic in a site-dependent manner, whereas tumour-specific PD-L1-expression is not prognostic in CRC.

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Section: Discussionmentioning

confidence: 99%

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis

et al. 2018

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“…In studies of multiple cancer types using immunohistochemical (IHC) analysis, PD-1 ligand 1 (PD-L1) protein expression on tumor cells and tumor-infiltrating immune cells have been reported to be associated with patient prognosis [6][7][8] and the response to PD-1/ PD-L1-targeted therapy [9,10]. Thus, PD-L1 protein expression is considered a potential biomarker of prognosis and therapeutic benefit.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, PD-L1 protein expression is considered a potential biomarker of prognosis and therapeutic benefit. However, in GC patients, the prognostic significance of PD-L1 protein expression in tumor cells and immune cells is still controversial [6][7][8][11][12][13][14], as is that of PD-1 [8,15] and CD8 [12,14,16] protein levels, probably because of different antibody clones, cutoff values for positivity and technical methods [6]. On the other hand, although a few studies have evaluated the association between PD-L1 mRNA levels and prognosis in GC [17,18], data acquired by mRNA analysis are quite limited.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Significance of PD-1, PD-L1 and CD8 Gene Expression Levels in Gastric Cancer

et al. 2020

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Introduction: Anti-programmed cell death 1 (PD-1) therapies have shown promising clinical activity against gastric cancer (GC). We evaluated the clinical significance of immune-related gene expression in GC tissues to better understand the tumor immune microenvironment. Methods: PD-1, PD-1 ligand 1 (PD-L1) and CD8 mRNA levels and clinicopathological factors, including survival, were examined by quantitative RT-PCR in 155 GC patients who underwent surgery. PD-1 and PD-L1 expression in tumor tissue from 24 GC patients was investigated by immunohistochemical analysis. Results: PD-1, PD-L1 and CD8 mRNA levels were significantly lower in tumor tissue than in normal tissue (p < 0.0001, p < 0.05, and p < 0.0001). GC patients with low PD-1, PD-L1 and CD8 mRNA levels had significantly poorer overall survival (OS) than those with high PD-1, PD-L1 and CD8 mRNA levels, respectively (p < 0.001, p < 0.01 and p < 0.05). Low PD-1, PD-L1 and CD8 mRNA levels were more significantly associated with poor prognosis in undifferentiated-type GC pa-tients than in differentiated-type GC patients (PD-1: differentiated p = 0.0071 vs. undifferentiated p = 0.0024; PD-L1: p = 0.6527 vs. p < 0.0001; CD8: p = 0.4465 vs. p < 0.05). Multivariate analysis showed that lymph node metastasis, peritoneal dissemination, distant metastasis, low PD-1 mRNA levels and low CD8 mRNA levels were independent prognostic factors for worse OS (low PD-1 mRNA level: OR 2.16, 95% CI 1.10-4.58, p < 0.05; low CD8 mRNA level: OR 2.55, 95% CI 1.12-6.90, p < 0.05). PD-1 and PD-L1 mRNA levels in immune cells were significantly associated with PD-1 and PD-L1 protein levels (both p < 0.05), respectively. Conclusions: PD-1, PD-L1 and CD8 mRNA levels may reflect antitumor immunity in GC, and low PD-1 and CD8 mRNA levels are potential predictive biomarkers for poor prognosis in GC patients who underwent surgery.

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“…Meanwhile, many studies have demonstrated that PD‐1, PD‐L1, or PD‐L2 protein expression are associated with survival of the solid tumors . In our previous study, we also found that the co‐expression of PD‐1 and PD‐L1 was a favorable prognostic marker in regard to the mortality risk of GC patients . However, the assessment of PD‐L1 status in tumors by the immunohistochemical (IHC) method still needs standardization .…”

Section: Introductionmentioning

confidence: 99%

“…[6][7][8][9] In our previous study, we also found that the co-expression of PD-1 and PD-L1 was a favorable prognostic marker in regard to the mortality risk of GC patients. 10 However, the assessment of PD-L1 status in tumors by the immunohistochemical (IHC) method still needs standardization. 11,12 Therefore, more stable and consistent markers associated with the PD-1 and PD-L1 pathway need to be identified for the prognostic evaluation of cancer.…”

Section: Introductionmentioning

confidence: 99%

Polymorphism of the programmed death‐ligand 1 gene is associated with its protein expression and prognosis in gastric cancer

Zhao

Jia

et al. 2018

J of Gastro and Hepatol

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Background and Aim While the incidence and mortality of gastric cancer (GC) remains high, and prognosis of GC remains poor, molecules in programmed death‐1 (PD‐1), programmed death‐ligand 1 (PD‐L1), and programmed death‐ligand 2 (PD‐L2) pathway are promising prognostic biomarker of GC. The polymorphisms on PD‐1, PD‐L1, and PD‐L2 may be associated with their protein expressions and affect the survival of GC patient. Methods Seven hundred fifty‐six GC patients who voluntarily supplied blood samples were enrolled in our study. We genotyped nine polymorphisms on PD‐1, PD‐L1, and PD‐L2, then evaluated the association of the single nucleotide polymorphisms with GC prognosis and analyzed the relationship between the PD‐1, PD‐L1, and PD‐L2 single nucleotide polymorphism genotypes and their protein expression. Results We found that PD‐L1 rs822336 CC genotype was independently associated with a better survival of all GC patients and those without postoperative chemotherapy (hazard ratio [HR] = 0.504, 95% confidence interval [CI] = 0.283–0.897 and HR = 0.385, 95% CI = 0.189–0.786). AA+AG genotype of rs2297136 in 3'UTR of the PD‐L1 was correlated with the protein expression of PD‐L1 protein both in patients overall and those without postoperative chemotherapy (P = 0.013 and P = 0.012). AA+AG genotype of rs2297136 served as an independent factor of better prognosis in patients without postoperative chemotherapy (HR = 0.348, 95% CI = 0.125–0.968). Conclusions Overall, PD‐L1 polymorphisms and protein expression were associated with the prognosis of patients with GC.

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PD-1 and PD-L1 co-expression predicts favorable prognosis in gastric cancer

Cited by 61 publications

References 54 publications

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis

Prognostic Significance of PD-1, PD-L1 and CD8 Gene Expression Levels in Gastric Cancer

Polymorphism of the programmed death‐ligand 1 gene is associated with its protein expression and prognosis in gastric cancer

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