***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Blockade of programmed death 1 ( PD-1 ) , an inhibitory receptor expressed by T cells , can overcome immune resistance . We assessed the antitumor activity and safety of BMS-936558 , an antibody that specifically blocks PD-1 . METHODS We enrolled patients with advanced melanoma , non-small-cell lung cancer , castration-resistant prostate cancer , or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks . Response was assessed after each 8-week treatment cycle . Patients received up to 12 cycles until disease progression or a complete response occurred . RESULTS A total of 296 patients received treatment through February 24 , 2012 .  Grade 3 or 4 drug-related adverse events occurred in 14 % of patients ; there were three deaths from pulmonary toxicity . No maximum tolerated dose was defined . Adverse events consistent with immune-related causes were observed . Among 236 patients in whom response could be evaluated , objective responses ( complete or partial responses ) were observed in those with non-small-cell lung cancer , melanoma , or renal-cell cancer .  Cumulative response rates ( all doses ) were 18 % among patients with non-small-cell lung cancer ( 14 of 76 patients ) , 28 % among patients with melanoma ( 26 of 94 patients ) , and 27 % among patients with renal-cell cancer ( 9 of 33 patients ) . Responses were durable ; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up . To assess the role of intratumoral PD-1 lig and ( PD-L1 ) expression in the modulation of the PD-1-PD-L1 pathway , immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients . Of 17 patients with PD-L1-negative tumors , none had an objective response ; 9 of 25 patients ( 36 % ) with PD-L1-positive tumors had an objective response ( P=0.006 ) . CONCLUSIONS Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer , melanoma , or renal-cell cancer ; the adverse-event profile does not appear to preclude its use . Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response . ( Funded by Bristol-Myers Squibb and others ; Clinical Trials.gov number , NCT00730639 . ) Therapies that target the programmed death-1 ( PD-1 ) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types . One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 lig and ( PD-L1 ) and its ligation to PD-1 on antigen-specific CD8 + T cells ( termed adaptive immune resistance ) . Here we show that pre-existing CD8 + T cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy . We analysed sample s from 46 patients with metastatic melanoma obtained before and during anti-PD-1 therapy ( pembrolizumab )  using quantitative immunohistochemistry , quantitative multiplex immunofluorescence , and next-generation sequencing for T-cell antigen receptors ( TCRs ) . In serially sample d tumours , patients responding to treatment showed proliferation of intratumoral CD8 + T cells that directly correlated with radiographic reduction in tumour size . Pre-treatment sample s obtained from responding patients showed higher numbers of CD8- , PD-1- and PD-L1-expressing cells at the invasive tumour margin and inside tumours , with close proximity between PD-1 and PD-L1 , and a more clonal TCR repertoire . Using multivariate analysis , we established a predictive model based on CD8 expression at the invasive margin and vali date d the model in an independent cohort of 15 patients . Our findings indicate that tumour regression after therapeutic PD-1 blockade requires pre-existing CD8 + T cells that are negatively regulated by PD-1/PD-L1-mediated adaptive immune resistance The development of human cancer is a multistep process characterized by the accumulation of genetic and epigenetic alterations that drive or reflect tumour progression . These changes distinguish cancer cells from their normal counterparts , allowing tumours to be recognized as foreign by the immune system . However , tumours are rarely rejected spontaneously , reflecting their ability to maintain an immunosuppressive microenvironment . Programmed death-lig and 1 ( PD-L1 ; also called B7-H1 or CD274 ) , which is expressed on many cancer and immune cells , plays an important part in blocking the ‘ cancer immunity cycle ’ by binding programmed death-1 ( PD-1 ) and B7.1 ( CD80 ) , both of which are negative regulators of T-lymphocyte activation . Binding of PD-L1 to its receptors suppresses T-cell migration , proliferation and secretion of cytotoxic mediators , and restricts tumour cell killing . The PD-L1–PD-1 axis protects the host from overactive T-effector cells not only in cancer but also during microbial infections . Blocking PD-L1 should therefore enhance anticancer immunity , but little is known about predictive factors of efficacy . This study was design ed to evaluate the safety , activity and biomarkers of PD-L1  inhibition using the engineered humanized antibody MPDL3280A . Here we show that across multiple cancer types , responses ( as evaluated by Response Evaluation Criteria in Solid Tumours , version 1.1 ) were observed in patients with tumours expressing high levels of PD-L1 , especially when PD-L1 was expressed by tumour-infiltrating immune cells . Furthermore , responses were associated with T-helper type 1 ( TH1 ) gene expression , CTLA4 expression and the absence of fractalkine ( CX3CL1 ) in baseline tumour specimens . Together , these data suggest that MPDL3280A is most effective in patients in which pre-existing immunity is suppressed by PD-L1 , and is re-invigorated on antibody treatment Purpose : The aberrant expression of programmed cell death 1 lig and s 1 and 2 ( PD-Ls ) on tumor cells dampens antitumor immunity , result ing 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 . Experimental Design : 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 r and omly 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 . Results : 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 vali date d in the independent data set . Conclusion : 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 BACKGROUND Programmed death 1 ( PD-1 ) protein , a T-cell coinhibitory receptor , and one of its lig and s , PD-L1 , play a pivotal role in the ability of tumor cells to evade the host 's immune system . Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in pre clinical models . METHODS In this multicenter phase 1 trial , we administered intravenous anti-PD-L1 antibody ( at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight ) to patients with selected advanced cancers .  Anti-PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression . RESULTS As of February 24 , 2012 , a total of 207 patients --75 with non-small-cell lung cancer , 55 with melanoma , 18 with colorectal cancer , 17 with renal-cell cancer , 17 with ovarian cancer , 14 with pancreatic cancer , 7 with gastric cancer , and 4 with breast cancer -- had received anti-PD-L1 antibody . The median duration of therapy was 12 weeks ( range , 2 to 111 ) . Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9 % of patients . Among patients with a response that could be evaluated , an objective response ( a complete or partial response ) was observed in 9 of 52 patients with melanoma , 2 of 17 with renal-cell cancer , 5 of 49 with non-small-cell lung cancer , and 1 of 17 with ovarian cancer . Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up . CONCLUSIONS Antibody-mediated blockade of PD-L1 induced durable tumor regression ( objective response rate of 6 to 17 % ) and prolonged stabilization of disease ( rates of 12 to 41 % at 24 weeks ) in patients with advanced cancers , including non-small-cell lung cancer , melanoma , and renal-cell cancer . ( Funded by Bristol-Myers Squibb and others ; Clinical Trials.gov number , NCT00729664 . ) 
    Output:
    
These results suggest that expression of PD-L1 is associated with worse survival in solid tumors .
However , the correlations between PD-L1 and prognosis are variant among different tumor types .