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      A prognosis and impact factor analysis of DC-CIK cell therapy for patients with hepatocellular carcinoma undergoing postoperative TACE

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          Abstract

          <p id="d7545865e368">Dendritic cell-cytokine-induced killer (DC-CIK) cell therapy has been experimentally implemented for enhancing anti-tumoral immunity in patients with hepatocellular carcinoma (HCC) undergoing postoperative transcatheter arterial chemoembolization (POTACE). We performed a retrospective study to evaluate the clinical efficacies of DC-CIK cell therapy and its correlations with several immune factors of the primary tumors. The overall survival time of HCC patients with HBV infection in the study group (POTACE plus DC-CIK cell therapy) was significantly longer than that of the control group (POTACE alone). The expression level of PD-L1 but not the tumor-infiltrated CD8 and CD4 T cells in the tumor tissues showed significant negative correlations with relapse-free survival (RFS) and overall survival (OS), which was also an independent prognostic factor for the five-years' suvival of patients with HCC receiving POTACE treatment. Furthermore, our study validated that PD-L1 expression was significantly inversely correlated with the survival time of HCC patients receiving POTACE plus DC-CIK cell therapy treatment. More importantly, DC-CIK cell therapy provided the best clinical benefits to HCC patients with the low PD-L1 expression receiving POTACE, which indicate that PD-L1 expression level can serve as a pivotal predictor for the therapeutic efficacy of DC-CIK cell therapy for HCC patients receiving POTACE treatment. </p>

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          Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma.

          Qiang Gao, Xiao-Ying Wang, Shuang-Jian Qiu … (2009)
          The aberrant expression of programmed cell death 1 ligands 1 and 2 (PD-Ls) on tumor cells dampens antitumor immunity, resulting in tumor immune evasion. In this study, we investigated the expression of PD-Ls in human hepatocellular carcinoma (HCC) to define their prognostic significance after curative surgery. Immunohistochemistry was used to investigate PD-Ls expression as well as granzyme B+ cytotoxic and FoxP3+ regulatory T cell infiltration on tissue microarrays containing 240 randomly selected HCC patients who underwent surgery. The results were further verified in an independent cohort of 125 HCC patients. PD-Ls expression on HCC cell lines was detected by Western blot assay. Patients with higher expression of PD-L1 had a significantly poorer prognosis than patients with lower expression. Although patients with higher expression of PD-L2 also had a poorer survival, the difference in recurrence was not statistically significant. Multivariate analysis identified tumor expression of PD-L1 as an independent predictor for postoperative recurrence. No correlation was found between PD-Ls expression and granzyme B+ lymphocyte infiltration, whereas a significant positive correlation was detected between PD-Ls expression and FoxP3+ lymphocyte infiltration. In addition, tumor-infiltrating cytotoxic and regulatory T cells were also independent prognosticators for both survival and recurrence. The prognostic value of PD-L1 expression was validated in the independent data set. Our data suggest for the first time that PD-L1 status may be a new predictor of recurrence for HCC patients and provide the rationale for developing a novel therapy of targeting the PD-L1/PD-1 pathway against this fatal malignancy.
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            High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation.

            Chuan-Yong Mu, Jian-An Huang, Ying Chen … (2011)
            The immunohistochemical analysis was used to evaluate the expression of PD-L1 in 109 non-small cell lung cancer (NSCLC) tissues and para-tumor tissues. Associations between expressed PD-L1 and tumor histological types, degree of differentiation, and lymph node metastasis were calculated, and overall survival was assessed. Meanwhile, immunohistochemistry and immunofluorescence double labeling technique were performed to detect the expressions of PD-L1, CD1α, and CD83 on TIDC of 20 lung cancer tissues, and the expression of PD-L1 in CD1α+DCs and CD83+DCs and their significances were also explored. We found that the expression rate of PD-L1 in NSCLC was associated with histological types and overall survival. Patients with either adenocarcinoma or survival time after surgery less than 3 years showed higher expression rate of PD-L1. Furthermore, Cox model analysis indicated that PD-L1 might be regarded as a poor prognostic factor. PD-L1 could be also detected in CD1α+ immature DC in NSCLC, indicating that as a class of key anti-tumor immunocyte in tumor microenvironment, DC expressing PD-L1 itself might play an important role in keeping its immature status and contributing to tumor cells immune escape and disease progression.
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              B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression.

              Jun Konishi, Koichi Yamazaki, Miyuki Azuma … (2004)
              B7-H1/PD-L1 (B7-H1) and B7-DC/PD-L2 (B7-DC) are ligands for the receptor PD-1, which is known to negatively regulate T-cell activation. In the present study, we investigated the expression of B7-H1 and B7-DC in tumor specimens of non-small cell lung cancer and their relationships with clinicopathological variables and postoperative survival. Furthermore, we examined the correlation between B7-H1 expression on tumor cells and the number of tumor-infiltrating lymphocytes (TILs) or PD-1 expression on TILs. The expression of B7-H1 and B7-DC in 52 surgically resected specimens of non-small cell lung cancer was evaluated immunohistochemically. Expression of B7-H1 and B7-DC was focally observed in all non-small cell lung cancer tumor specimens. No relationship was found between the expression of B7-H1 or B7-DC and clinicopathological variables or postoperative survival. However, in the same sections evaluated, significantly fewer TILs were identified in B7-H1-positive tumor regions than in B7-H1-negative tumor regions in a subset of five patients (P = 0.01). Moreover, the percentage of TILs expressing PD-1 was significantly lower in B7-H1-positive tumor regions than in B7-H1-negative tumor regions (P = 0.02). The expression of B7-H1 on tumor cells in local areas reciprocally correlated with the number of TILs, and this may contribute to negative regulation in antitumor immune responses in non-small cell lung cancer.
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                Author and article information

                Journal
                Title: Cancer Biology & Therapy
                Abbreviated Title: Cancer Biology & Therapy
                Publisher: Informa UK Limited
                ISSN (Print): 1538-4047
                ISSN (Electronic): 1555-8576
                Publication date Created: February 27 2018
                Publication date Created: June 03 2018
                Publication date (Electronic): March 06 2018
                Publication date (Print): June 03 2018
                Volume: 19
                Issue: 6
                Pages: 475-483
                Affiliations
                [1 ] Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
                [2 ] The Department of Radiology, Nanjing General Hospital, Nanjing Military Command of PLA, Nanjing, Jiangsu, China
                [3 ] Department of Pathology, School of Biomedical Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China
                [4 ] The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
                Article
                DOI: 10.1080/15384047.2018.1433501
                PMC ID: 5927715
                PubMed ID: 29400599
                SO-VID: 9505dd93-6793-407e-baea-bd3288424183
                Copyright © © 2018
                History

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