PD-L1 and Survival in Solid Tumors: A Meta-Analysis

Wu, Pin; Wu, Dang; Li, Lijun; Chai, Ying; Huang, Jian

doi:10.1371/journal.pone.0131403

Cited by 310 publications

(291 citation statements)

References 48 publications

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“…32,33 This notion is supported by the fact that PD-L1 positive tumor-infiltrating immune cells, but not PD-L1 positive tumor cells, have been documented to predict prognosis, though its implication may vary according to tumor type. 34,35 In contrast to other types of cancer, such as melanoma, renal cell cancer and lung cancer, PD-L1 expression have not been able to predict response to anti-PD-1 therapy in MMR deficient colorectal cancers. 11 This may be explained by a large proportion of tumors developing through the B2M-driven immune evasion mechanism or differences in PD-L1 expressing cell types.…”

Section: Discussionmentioning

confidence: 99%

Immunoprofiles of colorectal cancer from Lynch syndrome

et al. 2018

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Colorectal cancers associated with Lynch syndrome are characterized by defective mismatch repair, microsatellite instability, high mutation rates, and a highly immunogenic environment. These features define a subset of cancer with a favorable prognosis and high likelihood to respond to treatment with anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) drugs. With the aim to define immune-evasive mechanisms and a potential impact hereof in colorectal cancers from Lynch syndrome versus hereditary cases with retained mismatch repair function, we immunohistochemically and transcriptionally profiled 270 tumors. Lynch syndrome-associated tumors showed an overrepresentation of tumor-infiltrating CD3, CD8 and CD68 positive cells, loss of beta-2-microglobulin (B2M) and up-regulation of PD-L1 on tumor cells. The gene expression signature of Lynch syndrome tumors was characterized by upregulation of genes related to antigen processing and presentation, apoptosis, natural killer cell-mediated cytotoxicity, and T cell activation. Tumors with loss of B2M and up-regulation of PD-L1 showed distinctive immunogenic profiles. In summary, our data demonstrate a complex tumor-host interplay where B2M loss and PD-L1 up-regulation influence immunological pathways and clinical outcome in Lynch syndrome tumors. Immunological classification may thus aid in the preselection of colorectal cancers relevant for treatment with anti-PD-1/PD-L1 therapies.

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Section: Discussionmentioning

confidence: 99%

Immunoprofiles of colorectal cancer from Lynch syndrome

et al. 2018

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“…PD-L1 expression on tumor cells has been linked to a weakened host immune response and consequent poor prognosis in several malignancies, including melanoma and esophageal, gastric, hepatocellular and urothelial carcinomas, among others. 2,3 The role of PD-L1 expression in colorectal carcinoma is less clear, with some published studies reporting conflicting results as to whether PD-L1 expression indicates a better or worse prognosis. 4,5 In contrast to some malignancies such as melanoma, renal, and lung cancers, colorectal carcinoma generally demonstrates a very low response rate to PD-1 or PD-L1 blockade.…”

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confidence: 99%

PD-L1 expression in colorectal cancer is associated with microsatellite instability, BRAF mutation, medullary morphology and cytotoxic tumor-infiltrating lymphocytes

et al. 2016

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Programmed cell death 1 (PD-1) and its ligand (PD-L1) are key suppressors of the cytotoxic immune response. PD-L1 expression on tumor cells may be induced by the immune microenvironment, resulting in immune escape (adaptive immune resistance), and an adverse prognosis in many malignancies. In colorectal carcinoma the response to PD-1/PD-L1 inhibition is correlated with microsatellite instability. However, little is known about the clinicopathologic, molecular, and prognostic characteristics of colorectal carcinoma with PD-L1 expression. We performed immunohistochemistry for PD-L1 on 181 cases of colorectal carcinoma with known microsatellite instability and mutational status, and correlated PD-L1 expression with clinicopathologic features including tumor-infiltrating lymphocyte burden/immunophenotype, tumor mutational profile, and disease-specific survival. PD-L1 was expressed in tumors from 16 patients (9%) who were more often older (P = 0.006) and female (P = 0.035), with tumors exhibiting a larger size (P = 0.013), but lower stage (Po0.001). PD-L1 expression was associated with increased CD8 and TBET-positive tumor-infiltrating lymphocytes, medullary phenotype, poor differentiation, microsatellite instability, BRAF mutation (Po 0.001 for each), and a lower frequency of KRAS mutation (P = 0.012). On multivariate analysis, PD-L1 expression was associated with medullary morphology and frequent CD8-positive tumor-infiltrating lymphocytes, suggesting adaptive immune resistance. PD-L1 positivity was not predictive of survival in the entire cohort, but it was associated with a lower disease-specific survival within the microsatellite-instability high cohort. PD-L1 expression in colorectal carcinoma is associated with clinicopathologic and molecular features of the serrated pathway of colorectal carcinogenesis, and is associated with a worse outcome within microsatellite-unstable tumors. These findings support the role of PD-L1 expression in providing normally immunogenic colorectal carcinoma a means of immune evasion and a more aggressive biology, provide a potential mechanistic explanation for the favorable response of microsatellite-unstable colorectal carcinoma to PD-1/PD-L1 pathway blockade, and suggest potential predictive and prognostic roles of PD-L1 immunohistochemistry in colorectal carcinoma.

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“…6,7 The association between tumor PD-L1 expression and prognosis in patients with solid tumors, including NSCLC, has been explored, with findings suggesting a generally negative prognostic effect. 8 With respect to NSCLC, a retrospective analysis of NSCLC specimens using a prototype immunohistochemical (IHC) assay with the 22C3 antibody clone revealed that PD-L1 expression in tumors was not associated with improved prognosis compared with those without PD-L1 expression. 9,10 Furthermore, several recent meta-analyses have suggested a negative prognostic effect of tumor PD-L1 expression in this disease.…”

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confidence: 99%

Development of a Companion Diagnostic for Pembrolizumab in Non–Small Cell Lung Cancer Using Immunohistochemistry for Programmed Death Ligand-1

Dolled‐Filhart

Roach²,

Toland³

et al. 2016

Archives of Pathology &Amp; Laboratory Medicine

105

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Context.— Programmed death ligand-1 (PD-L1) expression by tumors may enable them to avoid immunosurveillance. Objective.— To develop a PD-L1 immunohistochemical assay using the 22C3 anti–PD-L1 murine monoclonal antibody on the Dako platform as a possible companion diagnostic for pembrolizumab in patients with non–small cell lung cancer. Design.— Tumor samples from 146 patients with non–small cell lung cancer treated with pembrolizumab in KEYNOTE-001 and for whom response data were available were scored according to their staining intensity by a single pathologist using 4 methods: percentage of tumor cells staining at any intensity (PS1), moderate/strong intensity (PS2), strong intensity (PS3), and H-score (PS1 + PS2 + PS3). The cutoff score for predicting response to pembrolizumab was determined using receiver operating characteristic analysis. Progression-free and overall survival were assessed in patients with measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (n = 146). Results.— The 4 scoring methods assessed performed similarly; PS1 with a 50% cutoff score is the simplest and easiest method to implement in practice. Response to pembrolizumab was observed in 19 of 44 patients (43%) with a PS1 score of 50% or higher and 8 of 102 patients (8%) with PS1 lower than 50% (odds ratio, 8.93). Median progression-free and overall survival was 4.0 months and not yet reached, respectively, for patients with a PS1 of 50% or higher, and 2.1 and 6.1 months, respectively, for those with PS1 lower than 50%. Conclusion.— The PD-L1 immunohistochemical assay shows the potential for enrichment of trial populations and as a companion diagnostic tool in non–small cell lung cancer.

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PD-L1 and Survival in Solid Tumors: A Meta-Analysis

Cited by 310 publications

References 48 publications

Immunoprofiles of colorectal cancer from Lynch syndrome

Immunoprofiles of colorectal cancer from Lynch syndrome

PD-L1 expression in colorectal cancer is associated with microsatellite instability, BRAF mutation, medullary morphology and cytotoxic tumor-infiltrating lymphocytes

Development of a Companion Diagnostic for Pembrolizumab in Non–Small Cell Lung Cancer Using Immunohistochemistry for Programmed Death Ligand-1

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