CD274 Expression

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Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Bladder Urothelial Carcinoma1
CD274 Expression	Atezolizumab	Predictive	B	Does Not Support Sensitivity Response	2	submitted	EID9886 Within a multicentre, open-label, phase 3 randomised control trial, investigation of the potential biomarker PD-L1 was found not to potentiate anti-tumor effects in response to atezolizumab in metasta… (full text at CIViC) PMID 29268948 · Powles et al., 2018 · Open in CIViC	civic
Gastric Carcinoma1
CD274 Expression	(prognostic)	Prognostic	B	Supports Better Outcome	3	accepted	EID1275 465 gastric cancer samples and 15 corresponding liver metastases underwent IHC for PD1/PD-L1 protein expression. PD-L1 positivity in tumor cells was defined by at least 2% tumor cells with membranous … (full text at CIViC) PMID 27009855 ·

Molecular profile

Therapy

Type

Level

Direction · significance

Rating (1–5)

Status

Evidence

Source

Bladder Urothelial Carcinoma1

CD274 Expression

Atezolizumab

Predictive

Does Not Support Sensitivity Response

submitted

EID9886

Within a multicentre, open-label, phase 3 randomised control trial, investigation of the potential biomarker PD-L1 was found not to potentiate anti-tumor effects in response to atezolizumab in metasta… (full text at CIViC)

PMID 29268948 · Powles et al., 2018 · Open in CIViC

civic

Gastric Carcinoma1

CD274 Expression

(prognostic)

Prognostic

Supports Better Outcome

accepted

EID1275

465 gastric cancer samples and 15 corresponding liver metastases underwent IHC for PD1/PD-L1 protein expression. PD-L1 positivity in tumor cells was defined by at least 2% tumor cells with membranous … (full text at CIViC)

PMID 27009855 ·

Head and Neck Squamous Cell Carcinoma1
CD274 Expression	Radiation Therapy	Predictive	B	Supports Resistance	4	accepted	EID3000 Radiation-resistant cell lines exhibited upregulation and increased activation of Axl, PI3 kinase signalling as well as increased expression of PD-L1. In 3 cohorts of HPV-negative head and neck squamo… (full text at CIViC) PMID 28476872 · Skinner et al., 2017 · Open in CIViC	civic

Head and Neck Squamous Cell Carcinoma1

CD274 Expression

Radiation Therapy

Predictive

Supports Resistance

accepted

EID3000

Radiation-resistant cell lines exhibited upregulation and increased activation of Axl, PI3 kinase signalling as well as increased expression of PD-L1. In 3 cohorts of HPV-negative head and neck squamo… (full text at CIViC)

PMID 28476872 · Skinner et al., 2017 · Open in CIViC

civic

Lung Non-Small Cell Carcinoma9
CD274 Expression	(prognostic)	Prognostic	B	Does Not Support Poor Outcome	4	accepted	EID701 This meta-analysis did not find a significant connection between expression of PD-L1 and overall survival in patients with NSCLC. PMID 26664143 · Zhong et al., 2015 · Open in CIViC	civic
CD274 Expression	(prognostic)	Prognostic	B	Supports Poor Outcome	2	accepted	EID975 74 patients with stage III NSCLC treated with concurrent chemoradiotherapy were retrospectively analyzed for PD-L1 expression and CD8+ tumour-infiltrating lymphocytes (TILs) density (IHC). CD8+ TIL de… (full text at CIViC) PMID 26771872 · Tokito et al., 2016 · Open in CIViC	civic
CD274 Expression	Atezolizumab	Predictive	B	Supports Sensitivity Response	4	accepted	EID1172 Exploratory biomarker analysis from a phase-II randomized trial comparing atezolizumab (PD-L1) and docetaxel in previously treated, advanced or metastatic non-small cell lung cancer. Baseline PD-L1 ex… (full text at CIViC) PMID 26970723 · Fehrenbacher et al., 2016 · Open in CIViC	civic
CD274 Expression	Atezolizumab	Predictive	B	Supports Sensitivity Response	3	submitted	EID9009 Within a phase one clinical trial, the response to atezolizumab from 938 patients with non-small cell carcinoma indicated high PD-L1 expression corresponded independently to response to atezolizumab o… (full text at CIViC) PMID 30297397 · Kowanetz et al., 2018 · Open in CIViC	civic
CD274 Expression	Nivolumab + PembrolizumabSubstitutes	Predictive	B	Supports Sensitivity Response	4	accepted	EID743 Based on a meta-analysis of 20 trials (1475 patients), PD-L1 expression was associated with a higher ORR rate in patients with NSCLC. Active drugs were Nivolumab and Pembrolizumab, PD-1 receptor targe… (full text at CIViC) PMID 26086854 · Carbognin et al., 2015 · Open in CIViC	civic
CD274 Expression	Atezolizumab + Avelumab + Nivolumab + PembrolizumabSubstitutes	Predictive	B	Supports Sensitivity Response	4	accepted	EID1167 Meta-Analysis of PD-L1 (CD274) Expression Status in 914 patients (7 studies) and response to PD-1/PD-L1 monoclonal antibodies. Patients with PD-L1 positive tumors (PD-L1 tumor cell staining ≥1%), had … (full text at CIViC) PMID 26918451 · Passiglia et al., 2016 · Open in CIViC	civic
CD274 Expression	Atezolizumab + Avelumab + Durvalumab + Nivolumab + PembrolizumabSubstitutes	Predictive	B	Supports Sensitivity Response	3	accepted	EID4857 In this meta-analysis of 14 studies with 2857 patients, the immunotherapy response rate was higher among PD-L1-positive patients (RR: 2.19, 95% CI: 1.63-2.94). PD-L1 expression was also related to bet… (full text at CIViC) PMID 28472902 · Aguiar et al., 2017 · Open in CIViC	civic
CD274 Expression	Pembrolizumab	Predictive	B	Supports Sensitivity Response	3	accepted	EID1733 This open-label, randomized, phase-3 clinical trial compared pembrolizumab to chemotherapy in treating NSCLC patients with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation o… (full text at CIViC) PMID 27718847 · Reck et al., 2016 · Open in CIViC	civic
CD274 Expression	Pembrolizumab	Predictive	B	Supports Sensitivity Response	4	accepted	EID5811 PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy of pembrolizumab. PMID 25891174 · Garon et al., 2015 · Open in CIViC	civic

Lung Non-Small Cell Carcinoma9

CD274 Expression

(prognostic)

Prognostic

Does Not Support Poor Outcome

accepted

EID701

This meta-analysis did not find a significant connection between expression of PD-L1 and overall survival in patients with NSCLC.

PMID 26664143 · Zhong et al., 2015 · Open in CIViC

civic

CD274 Expression

(prognostic)

Prognostic

Supports Poor Outcome

accepted

EID975

74 patients with stage III NSCLC treated with concurrent chemoradiotherapy were retrospectively analyzed for PD-L1 expression and CD8+ tumour-infiltrating lymphocytes (TILs) density (IHC). CD8+ TIL de… (full text at CIViC)

PMID 26771872 · Tokito et al., 2016 · Open in CIViC

civic

CD274 Expression

Atezolizumab

Predictive

Supports Sensitivity Response

accepted

EID1172

Exploratory biomarker analysis from a phase-II randomized trial comparing atezolizumab (PD-L1) and docetaxel in previously treated, advanced or metastatic non-small cell lung cancer. Baseline PD-L1 ex… (full text at CIViC)

PMID 26970723 · Fehrenbacher et al., 2016 · Open in CIViC

civic

CD274 Expression

Atezolizumab

Predictive

Supports Sensitivity Response

submitted

EID9009

Within a phase one clinical trial, the response to atezolizumab from 938 patients with non-small cell carcinoma indicated high PD-L1 expression corresponded independently to response to atezolizumab o… (full text at CIViC)

PMID 30297397 · Kowanetz et al., 2018 · Open in CIViC

civic

CD274 Expression

Nivolumab + PembrolizumabSubstitutes

Predictive

Supports Sensitivity Response

accepted

EID743

Based on a meta-analysis of 20 trials (1475 patients), PD-L1 expression was associated with a higher ORR rate in patients with NSCLC. Active drugs were Nivolumab and Pembrolizumab, PD-1 receptor targe… (full text at CIViC)

PMID 26086854 · Carbognin et al., 2015 · Open in CIViC

civic

CD274 Expression

Atezolizumab + Avelumab + Nivolumab + PembrolizumabSubstitutes

Predictive

Supports Sensitivity Response

accepted

EID1167

Meta-Analysis of PD-L1 (CD274) Expression Status in 914 patients (7 studies) and response to PD-1/PD-L1 monoclonal antibodies. Patients with PD-L1 positive tumors (PD-L1 tumor cell staining ≥1%), had … (full text at CIViC)

PMID 26918451 · Passiglia et al., 2016 · Open in CIViC

civic

CD274 Expression

Atezolizumab + Avelumab + Durvalumab + Nivolumab + PembrolizumabSubstitutes

Predictive

Supports Sensitivity Response

accepted

EID4857

In this meta-analysis of 14 studies with 2857 patients, the immunotherapy response rate was higher among PD-L1-positive patients (RR: 2.19, 95% CI: 1.63-2.94). PD-L1 expression was also related to bet… (full text at CIViC)

PMID 28472902 · Aguiar et al., 2017 · Open in CIViC

civic

CD274 Expression

Pembrolizumab

Predictive

Supports Sensitivity Response

accepted

EID1733

This open-label, randomized, phase-3 clinical trial compared pembrolizumab to chemotherapy in treating NSCLC patients with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation o… (full text at CIViC)

PMID 27718847 · Reck et al., 2016 · Open in CIViC

civic

CD274 Expression

Pembrolizumab

Predictive

Supports Sensitivity Response

accepted

EID5811

PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy of pembrolizumab.

PMID 25891174 · Garon et al., 2015 · Open in CIViC

civic

Lung Squamous Cell Carcinoma1
CD274 Expression	(prognostic)	Prognostic	B	Supports Better Outcome	3	accepted	EID702 In this study, PD-L1 expression (measured by IHC) was associated with better overall survival in the subgroup of Lung Squamous Cell Carcinomas (149 of 321 patients in the study). PMID 26313362 · Schmidt et al., 2015 · Open in CIViC	civic

Lung Squamous Cell Carcinoma1

CD274 Expression

(prognostic)

Prognostic

Supports Better Outcome

accepted

EID702

In this study, PD-L1 expression (measured by IHC) was associated with better overall survival in the subgroup of Lung Squamous Cell Carcinomas (149 of 321 patients in the study).

PMID 26313362 · Schmidt et al., 2015 · Open in CIViC

civic

Malignant Breast Neoplasm3
CD274 Expression	(diagnostic)	Diagnostic	A	Supports Positive	4	submitted	EID11484 The results and published literature suggest that in addition to guiding targeted therapy selection, comprehensive genomic profiling shows the potential to identify genomic alterations linked to respo… (full text at CIViC) PMID 33314633 · Sivapiragasam et al., 2021 · Open in CIViC	civic
CD274 Expression	(prognostic)	Prognostic	B	Supports Poor Outcome	2	accepted	EID4844 A meta-analysis of the role of PD-L1 expression in breast cancer found nine relevant studies with a total 8583 patients. PD-L1 expression was found to be associated with several poor prognostic indica… (full text at CIViC) PMID 28079291 · Wang et al., 2017 · Open in CIViC	civic
CD274 Expression	(prognostic)	Prognostic	B	Supports Poor Outcome	3	accepted	EID4855 In this meta-analysis, 5 studies totalling 2,546 cases were combined to assess the prognostic association of PD-L1 expression in breast cancer. The combined hazard ratio (HR) for PD-L1 overexpression … (full text at CIViC) PMID 28430626 · Zhang et al., 2017 · Open in CIViC	civic

Malignant Breast Neoplasm3

CD274 Expression

(diagnostic)

Diagnostic

Supports Positive

submitted

EID11484

The results and published literature suggest that in addition to guiding targeted therapy selection, comprehensive genomic profiling shows the potential to identify genomic alterations linked to respo… (full text at CIViC)

PMID 33314633 · Sivapiragasam et al., 2021 · Open in CIViC

civic

CD274 Expression

(prognostic)

Prognostic

Supports Poor Outcome

accepted

EID4844

A meta-analysis of the role of PD-L1 expression in breast cancer found nine relevant studies with a total 8583 patients. PD-L1 expression was found to be associated with several poor prognostic indica… (full text at CIViC)

PMID 28079291 · Wang et al., 2017 · Open in CIViC

civic

CD274 Expression

(prognostic)

Prognostic

Supports Poor Outcome

accepted

EID4855

In this meta-analysis, 5 studies totalling 2,546 cases were combined to assess the prognostic association of PD-L1 expression in breast cancer. The combined hazard ratio (HR) for PD-L1 overexpression … (full text at CIViC)

PMID 28430626 · Zhang et al., 2017 · Open in CIViC

civic

Malignant Nasopharyngeal Neoplasm1
CD274 Expression	Nivolumab	Predictive	B	Supports Sensitivity Response	1	submitted	EID9010 In a Clinic Phase 2 Consortium, 44 patients with metastatic nasopharyngeal carcinoma had an overall response rate (ORR) to nivolumab of 20.5%; 1 complete response lasting over 12 months; 8 partial res… (full text at CIViC) PMID 29584545 · Ma et al., 2018 · Open in CIViC	civic

Malignant Nasopharyngeal Neoplasm1

CD274 Expression

Nivolumab

Predictive

Supports Sensitivity Response

submitted

EID9010

In a Clinic Phase 2 Consortium, 44 patients with metastatic nasopharyngeal carcinoma had an overall response rate (ORR) to nivolumab of 20.5%; 1 complete response lasting over 12 months; 8 partial res… (full text at CIViC)

PMID 29584545 · Ma et al., 2018 · Open in CIViC

civic

Malignant Neoplasm3
CD274 Expression	(prognostic)	Prognostic	B	Supports Better Outcome	2	accepted	EID4856 PD-L1 is not only expressed in tumor cells (TCs) but also upregulated in tumor-infiltrating immune cells (TIICs). This meta-analysis evaluated the prognostic value of PD-L1 expression in TIICs in diff… (full text at CIViC) PMID 28453554 · Zhao et al., 2017 · Open in CIViC	civic
CD274 Expression	(prognostic)	Prognostic	B	Supports Poor Outcome	4	accepted	EID5507 A meta analysis of 60 research studies involving 10,310 solid tumors indicated that CD274 over expression results in poor overall survival (HR = 1.58, P <.001) and poor disease free/progression free s… (full text at CIViC) PMID 28471952 · Wang et al., 2017 · Open in CIViC	civic
CD274 Expression	Nivolumab	Predictive	B	Supports Sensitivity Response	2	accepted	EID1517 Trial NCT00730639 tested monoclonal antibody nivolumab against the PD-1 immune checkpoint receptor in pretreated patients with various cancer types. PD-L1 expression was tested in 42 patients by ICH f… (full text at CIViC) PMID 22658127 · Topalian et al., 2012 · Open in CIViC	civic

Malignant Neoplasm3

CD274 Expression

(prognostic)

Prognostic

Supports Better Outcome

accepted

EID4856

PD-L1 is not only expressed in tumor cells (TCs) but also upregulated in tumor-infiltrating immune cells (TIICs). This meta-analysis evaluated the prognostic value of PD-L1 expression in TIICs in diff… (full text at CIViC)

PMID 28453554 · Zhao et al., 2017 · Open in CIViC

civic

CD274 Expression

(prognostic)

Prognostic

Supports Poor Outcome

accepted

EID5507

A meta analysis of 60 research studies involving 10,310 solid tumors indicated that CD274 over expression results in poor overall survival (HR = 1.58, P <.001) and poor disease free/progression free s… (full text at CIViC)

PMID 28471952 · Wang et al., 2017 · Open in CIViC

civic

CD274 Expression

Nivolumab

Predictive

Supports Sensitivity Response

accepted

EID1517

Trial NCT00730639 tested monoclonal antibody nivolumab against the PD-1 immune checkpoint receptor in pretreated patients with various cancer types. PD-L1 expression was tested in 42 patients by ICH f… (full text at CIViC)

PMID 22658127 · Topalian et al., 2012 · Open in CIViC

civic

Melanoma3
CD274 Expression	Ipilimumab + NivolumabCombination	Predictive	B	Does Not Support Sensitivity Response	3	accepted	EID1615 A clinical trial of 86 patients evaluated concurrent (n=53) or sequential (n=33) treatment of ipilimumab (anti-CTLA4) and nivolumab (anti-PD1). In the concurrent regimen cohort, 65% of patients showed… (full text at CIViC) PMID 23724867 · Wolchok et al., 2013 · Open in CIViC	civic
CD274 Expression	Nivolumab + PembrolizumabSubstitutes	Predictive	B	Supports Sensitivity Response	4	accepted	EID704 Based on a meta-analysis of 20 trials (1475 patients), of which 7 studies (636 patients) included melanoma, PD-L1 expression was associated with a higher ORR rate in patients with melanoma. Active dru… (full text at CIViC) PMID 26086854 · Carbognin et al., 2015 · Open in CIViC	civic
CD274 Expression	Nivolumab + PembrolizumabSubstitutes	Predictive	B	Supports Sensitivity Response	1	submitted	EID9008 Within a preclinical trial, 37 patients with metastatic melanoma showed a limited number of cases that responded to anti-PD-1 antibodies in correlation to higher immunohistochemical PD-L1 expression. … (full text at CIViC) PMID 27491654 · Cho et al., 2016 · Open in CIViC	civic

Melanoma3

CD274 Expression

Ipilimumab + NivolumabCombination

Predictive

Does Not Support Sensitivity Response

accepted

EID1615

A clinical trial of 86 patients evaluated concurrent (n=53) or sequential (n=33) treatment of ipilimumab (anti-CTLA4) and nivolumab (anti-PD1). In the concurrent regimen cohort, 65% of patients showed… (full text at CIViC)

PMID 23724867 · Wolchok et al., 2013 · Open in CIViC

civic

CD274 Expression

Nivolumab + PembrolizumabSubstitutes

Predictive

Supports Sensitivity Response

accepted

EID704

Based on a meta-analysis of 20 trials (1475 patients), of which 7 studies (636 patients) included melanoma, PD-L1 expression was associated with a higher ORR rate in patients with melanoma. Active dru… (full text at CIViC)

PMID 26086854 · Carbognin et al., 2015 · Open in CIViC

civic

CD274 Expression

Nivolumab + PembrolizumabSubstitutes

Predictive

Supports Sensitivity Response

submitted

EID9008

Within a preclinical trial, 37 patients with metastatic melanoma showed a limited number of cases that responded to anti-PD-1 antibodies in correlation to higher immunohistochemical PD-L1 expression. … (full text at CIViC)

PMID 27491654 · Cho et al., 2016 · Open in CIViC

civic

Merkel Cell Carcinoma1
CD274 Expression	Pembrolizumab	Predictive	B	Does Not Support Sensitivity Response	2	accepted	EID1578 Patients with Merkel Cell Carcinoma (n=26) were enrolled to receive pembrolizumab. Of these patients, 25 were evaluated for response rate to pembrolizumab and PD-L1 (CD274) expression. The response ra… (full text at CIViC) PMID 27093365 · Nghiem et al., 2016 · Open in CIViC	civic

Merkel Cell Carcinoma1

CD274 Expression

Pembrolizumab

Predictive

Does Not Support Sensitivity Response

accepted

EID1578

Patients with Merkel Cell Carcinoma (n=26) were enrolled to receive pembrolizumab. Of these patients, 25 were evaluated for response rate to pembrolizumab and PD-L1 (CD274) expression. The response ra… (full text at CIViC)

PMID 27093365 · Nghiem et al., 2016 · Open in CIViC

civic

Ovarian Serous Adenocarcinoma1
CD274 Expression	(prognostic)	Prognostic	B	Supports Better Outcome	3	accepted	EID703 High expression of PD-L1 and PD-1 were associated with a favorable prognosis in patients with high grade serous ovarian carcinoma (n = 215 cases). PMID 26625204 · Darb-Esfahani et al., 2016 · Open in CIViC	civic

Ovarian Serous Adenocarcinoma1

CD274 Expression

(prognostic)

Prognostic

Supports Better Outcome

accepted

EID703

High expression of PD-L1 and PD-1 were associated with a favorable prognosis in patients with high grade serous ovarian carcinoma (n = 215 cases).

PMID 26625204 · Darb-Esfahani et al., 2016 · Open in CIViC

civic

Thyroid Gland Papillary Carcinoma1
CD274 Expression	(prognostic)	Prognostic	B	Supports Poor Outcome	3	accepted	EID1274 Immunohistochemical analyses of PD-L1 protein was retrospectively performed on 251 archived FFPE surgical tissues (66 benign thyroid nodules and 185 papillary thyroid carcinomas PTC, E1L3N antibody). … (full text at CIViC) PMID 27086918 · Chowdhury et al., 2016 · Open in CIViC	civic

Thyroid Gland Papillary Carcinoma1

CD274 Expression

(prognostic)

Prognostic

Supports Poor Outcome

accepted

EID1274

Immunohistochemical analyses of PD-L1 protein was retrospectively performed on 251 archived FFPE surgical tissues (66 benign thyroid nodules and 185 papillary thyroid carcinomas PTC, E1L3N antibody). … (full text at CIViC)

PMID 27086918 · Chowdhury et al., 2016 · Open in CIViC

civic

Evidence by cancer (26 items)

Clinical significance (0)