Predictive biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy

Meng, Xiangjiao; Huang, Zhaoqin; Teng, Feifei; Xing, Ligang; Yu, Jinming

doi:10.1016/j.ctrv.2015.11.001

Cited by 357 publications

(310 citation statements)

References 66 publications

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“…Another reported predictive factor for response to anti PD-1 agents is PD-L1 expression before treatment, but this remains a matter of debate owing to the dynamic process of PD-L1 expression, the multiplicity of detection methods and the use of different cutoff values. 17 Moreover, the predictive value of PD-L1 expression also differs between tumor subtypes and the monoclonal antibody used. As an example, PD-L1 status alone does not seem to be useful in the selection of melanoma patients for nivolumab.…”

mentioning

confidence: 99%

Analysis of PD-L1, T-cell infiltrate and HLA expression in chondrosarcoma indicates potential for response to immunotherapy specifically in the dedifferentiated subtype

et al. 2016

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Therapies targeting the programmed cell death 1 (PD-1) or its ligand (PD-L1) promote antitumor T-cell activity, leading to unprecedented long-lasting tumor responses in some advanced cancers. Because of radiotherapy and chemotherapy resistance, no effective treatments have been defined for advanced chondrosarcomas. We here report an immunohistochemical analysis of PD-L1 expression in a large series of conventional, mesenchymal, clear cell and dedifferentiated chondrosarcomas using tissue microarrays. In the PD-L1-positive tumors, we analyzed the immune microenvironment (T-cell and macrophage infiltration as well as HLA class I expression) using whole sections. PD-L1 expression was absent in conventional (n = 119), mesenchymal (n = 19) and clear cell (n = 20) chondrosarcomas. Forty-one percent (9 of the 22) of dedifferentiated chondrosarcomas displayed PD-L1 positivity. These results were confirmed in an independent cohort using whole tissue sections of dedifferentiated chondrosarcomas in which PD-L1 expression was detected in 52% (11 of the 21) of cases. PD-L1 expression was exclusively found in the dedifferentiated component and expression positively correlated with other immune parameters such as high number of tumor-infiltrating lymphocytes (P = 0.014) and positive HLA class I expression (P = 0.024) but not with patient overall survival (P = 0. Chondrosarcomas constitute a malignant group of cartilaginous matrix-producing neoplasms, with diverse morphological features and clinical behavior. 1 Conventional chondrosarcoma is the second most common primary bone malignancy after osteosarcoma and can be categorized according to their location into central (85%) and peripheral chondrosarcomas (15%). Their histology is similar, with atypical chondrocytes and abundant extracellular matrix, but they differ at the genetic level. Notably, mutations in isocitrate dehydrogenase (IDH) 1 and 2 are found in approximately half of conventional central chondrosarcomas while mutations in genes encoding exostosin (EXT) 1 and 2 characterize peripheral chondrosarcomas. 2,3 Histological grade is strongly correlated with clinical prognosis with a 10-year survival rate of 83% for atypical cartilaginous tumor/grade I but only 29% for grade III. In addition to conventional chondrosarcoma, several rare subtypes of chondrosarcoma are discerned (dedifferentiated, mesenchymal and clear cell), together constituting 10-15% of all chondrosarcomas. Clear cell chondrosarcoma is a low-grade malignant tumor with a 10-year survival rate reported around 90% while dedifferentiated and mesenchymal chondrosarcoma are both highly malignant, with frequent occurrence of distant metastases and o30% survival at 5 and 10 years, respectively. 4

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confidence: 99%

Analysis of PD-L1, T-cell infiltrate and HLA expression in chondrosarcoma indicates potential for response to immunotherapy specifically in the dedifferentiated subtype

et al. 2016

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“…44,45 A wide variety of cancers express PD-L1 including melanoma, lung, renal, bladder, esophageal, gastric and other cancers. 46 T cells are activated by tumor-specific antigens. Activated T cells proliferate and attack antigen-expressing tumor cells, ultimately destroying them.…”

Section: The Product Of Interestmentioning

confidence: 99%

“…A number of studies have focused on the role of immunohistochemical expression of PD-L1 in tumor cells. 46 A meta-analysis to determine the predictive value of tumor cell PD-L1 expression involving 20 clinical trials that enrolled a total of 1475 patients revealed a higher response rate in patients with PD-L1-positive tumors (34% vs. 20%, p < 0.0001). 78 The absolute difference between response rate in PD-L1-positive and PD-L1-negative cases treated with nivolumab was 16.4%.…”

Section: Development Of Predictive Biomarkersmentioning

confidence: 99%

Nivolumab, anti-programmed death-1 (PD-1) monoclonal antibody immunotherapy: Role in advanced cancers

Rajan

Kim

Heery

et al. 2016

Human Vaccines & Immunotherapeutics

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The development of immune checkpoint inhibitors has altered the landscape of treatment of advanced cancers. These drugs are well tolerated and have shown clinical activity against a wide variety of solid tumors and hematological malignancies. The durability of response is particularly impressive when compared to other forms of systemic therapy. Nivolumab (Opdivo) is an IgG4 antibody that causes immune checkpoint blockade by diminishing inhibitory signaling through the programmed death receptor-1 pathway. It is approved for treatment of recurrent non-small cell lung cancer, melanoma, and renal cell carcinoma. Efforts to identify biomarkers of response to nivolumab are ongoing. Clinical trials are also being conducted to determine the benefits of combining nivolumab with other forms of treatment including chemotherapy, molecular-targeted therapy, radiation therapy, and other forms of immune therapy. This review outlines the clinical trials that have led to the emergence of nivolumab as a treatment option for patients with advanced cancers.

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“…However, an important issue is how to identify patients likely to benefit from PD-1/PD-L1 inhibitors. The findings of recent studies indicate that PD-L1 expression levels have emerged as a predictive biomarker useful for stratifying patients with NSCLC who are receiving PD-1/PD-L1 therapeutic agents (10). Each PD-1/PD-L1 inhibitor has been tested with a companion diagnostic assay or complementary diagnostic assay using different PD-L1 antibodies (clone 28-8, clone 22C3, clone SP142 and clone SP263), protocols, or cut-offs for PD-L1 positivity (see in Table 2).…”

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confidence: 99%

PD-L1 protein expression in non-small cell lung cancer based on different immunohistochemical antibodies

et al. 2017

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Predictive biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy

Cited by 357 publications

References 66 publications

Analysis of PD-L1, T-cell infiltrate and HLA expression in chondrosarcoma indicates potential for response to immunotherapy specifically in the dedifferentiated subtype

Analysis of PD-L1, T-cell infiltrate and HLA expression in chondrosarcoma indicates potential for response to immunotherapy specifically in the dedifferentiated subtype

Nivolumab, anti-programmed death-1 (PD-1) monoclonal antibody immunotherapy: Role in advanced cancers

PD-L1 protein expression in non-small cell lung cancer based on different immunohistochemical antibodies

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