10
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Association between PD-L1 Expression on Tumour-Infiltrating Lymphocytes and Overall Survival in Patients with Gastric Cancer

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Purpose Targeting of the PD-1/PD-L1 signalling pathway is a promising treatment strategy in several cancers. The aim of this study was to assess the expression of PD-L1 on tumour cells and tumour-infiltrating lymphocytes (TILs) in gastric cancer (GC) and its prognostic impact.

          Materials and Methods A total of 240 patients who were diagnosed with GC at Sun Yat-sen University Cancer Centre (SYSUCC) from May 2008 to December 2013 were included in this study. PD-L1 expression was detected by immunohistochemistry (IHC) in all GC tumour specimens. The Cox proportional hazard regression model was used to assess the association between PD-L1 expression and overall survival (OS).

          Results The positive rates of PD-L1 expression on tumour cells and TILs were 74.8% and 65.8%, respectively. Patients with poor tumour differentiation had higher positive rates of PD-L1 expression on tumour cells (p=0.023). There was no significant association between PD-L1 expression on tumour cells and other clinicopathological data. In TILs, PD-L1 expression was significantly higher in patients who underwent surgery (p=0.031) and were in the late stage (p=0.021) than those without surgery and in the early stage. Patients with positive PD-L1 expression on TILs had a significantly shorter five-year OS than those with negative PD-L1 expression (14.2 vs 18.3; p=0.001); therefore, PD-L1 expression on TILs is an independent prognostic factor. However, PD-L1 expression on tumour cells is not associated with OS (p=0.945).

          Conclusion Our findings suggest that PD-L1 expression on TILs may be a predictive factor for immunotherapy of PD-1/PD-L1 pathway inhibitors.

          Related collections

          Most cited references18

          • Record: found
          • Abstract: found
          • Article: not found

          Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma.

          : Melanoma tends to be refractory to various immunotherapies because of tumor-induced immunosuppression. To investigate the mechanism underlining the immunosuppression of melanoma patients, the authors focused on programmed cell death-1 (PD-1)/PD-1 ligand 1 (PD-L1) interaction between tumor cells and T cells. : Melanoma specimens were collected from 59 primary tumors, 16 lymph nodes, and 4 lesions of in-transit metastasis. Specimens stained with anti-PD-L1 monoclonal antibodies were digitalized to jpg files. To evaluate the intensity of PD-L1 expression, histograms were used, and the red density (RD) was measured. PD-1 expression on T cells was analyzed in blood samples from 10 patients who had stage IV melanoma and in 4 samples of in-transit metastases. : Twenty-five patients comprised the "low" PD-L1 expression group (RD value, or =90). Breslow tumor thickness in the high-expression group was significantly higher than in the low-expression group. Univariate and multivariate analyses revealed that the overall survival rate of the high-expression group was significantly lower than that of the low-expression group. In all patients with stage IV disease who were examined, both CD8-positive and CD4-positive T cells had significantly higher PD-1 expression levels in the peripheral blood. Tumor-infiltrating T cells expressed high levels of PD-1, and its expression was elevated further during the clinical course. : The current results indicated that there is a correlation between the degree of PD-L1 expression and the vertical growth of primary tumors in melanoma. Multivariate analysis demonstrated that PD-L1 expression is an independent prognostic factor for melanoma. Cancer 2010. (c) 2010 American Cancer Society.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            In situ tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas.

            Blockade of the PD-1/PD-L1 axis emerged as a promising new therapeutic option for cancer that has resulted in lasting responses in metastatic renal, lung carcinomas, and melanomas. Tumor PD-L1 protein expression may predict response to drugs targeting this pathway. Measurement of PD-L1 protein is limited by the lack of standardized immunohistochemical methods and variable performance of antibodies. Our goal was to correlate PD-L1 mRNA expression with clinical variables in primary breast carcinomas. The fluorescent RNAscope paired-primer assay was used to quantify in situ PD-L1 mRNA levels in 636 stage I-III breast carcinomas on two sets of tissue microarrays [YTMA128 (n = 238) and YTMA201 (n = 398)]. Tumor-infiltrating lymphocytes (TIL) were assessed by hematoxylin/eosin stain and quantitative fluorescence. On YTMA128 and YTMA201, 55.7% and 59.5% of cases showed PD-L1 mRNA expression, respectively. Higher PD-L1 mRNA expression was significantly associated with increased TILs (P = 0.04) but not with other clinical variables. Elevated TILs (scores 2 and 3+) occurred in 16.5% on YTMA128 and 14.8% on YTMA201 and was associated with estrogen receptor-negative status (P = 0.01 on YTMA128 and 0.0001 on YTMA201). PD-L1 mRNA expression was associated with longer recurrence-free survival (log-rank P = 0.01), which remained significant in multivariate analysis including age, tumor size, histologic grade, nodal metastasis, hormone receptor, HER2 status, and the extent of TILs (HR, 0.268; CI, 0.099-0.721; P = 0.009). PD-L1 mRNA expression is identified in nearly 60% of breast tumors and it is associated with increased TILs and improved recurrence-free survival. These observations support the evaluation of PD-1/PD-L1-targeted therapies in breast cancer. ©2014 American Association for Cancer Research.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer.

              There are few data on the clinical implications of immunosuppressive protein expression in tumors and immune cell infiltration within the tumor microenvironment in patients with gastric cancer (GC).
                Bookmark

                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2017
                3 June 2017
                : 8
                : 9
                : 1579-1585
                Affiliations
                [1 ]Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China;
                [2 ]State Key Laboratory of Oncology in South China, Guangzhou, China;
                [3 ]Collaborative Innovation Center for Cancer Medicine, Guangzhou, China;
                [4 ]Department of Medical Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhu Hai, China.
                Author notes
                ✉ Corresponding authors: Li Zhang, MD, Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, P. R. China. E-mail: zhangli6@ 123456mail.sysu.edu.cn Peijian Peng, MD, PhD, Department of Medical Oncology, The Fifth Affiliated Hospital of Sun-Yat-Sen University, 52 Mei Hua Road East, Zhu Hai, 519000, Guangdong Province, China. E-mail: pengpjian@ 123456163.com

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                jcav08p1579
                10.7150/jca.18729
                5535713
                28775777
                226e56e3-c650-44c7-9ed1-0b2e70fa992a
                © Ivyspring International Publisher

                This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 13 December 2016
                : 31 March 2017
                Categories
                Research Paper

                Oncology & Radiotherapy
                gastric cancer,pd-l1,tils.
                Oncology & Radiotherapy
                gastric cancer, pd-l1, tils.

                Comments

                Comment on this article