Programmed death ligand-1 (PD-L1) as a predictive marker for immunotherapy in solid tumours: a guide to immunohistochemistry implementation and interpretation

Paver, Elizabeth; Cooper, Wendy A.; Colebatch, Andrew J.; Ferguson, Peter M.; Hill, Sean K.; Lum, Trina; Shin, Joo‐Shik; O’Toole, Sandra A.; Anderson, Lyndal; Scolyer, Richard A.; Gupta, Ruta

doi:10.1016/j.pathol.2020.10.007

Cited by 140 publications

(122 citation statements)

References 105 publications

(121 reference statements)

Supporting

Mentioning

122

Contrasting

Order By: Relevance

“…However, what is even more interesting in our experience is that sPDL-1 levels appear to represent a good surrogate of a response criteria to systemic therapy administered in metastatic CCRCC. In this context, there are many limitations to consider when deciding to treat CCRCC patients with immune checkpoint inhibitors based on the immunohistochemical detection of PD-1/PD-L1 positivity alone [11,27], while the search of markers to anticipate the response to immunotherapy continues [42][43][44]. A new trial (UMIN000027873) has been recently launched to evaluate the therapeutic effect of nivolumamb as a second-line therapy for advanced CCRCC based on the concentrations of serum sPD-L1.…”

Section: Discussionmentioning

confidence: 99%

Soluble PD-L1 Is an Independent Prognostic Factor in Clear Cell Renal Cell Carcinoma

Larrinaga

Solano-Iturri

Errarte

et al. 2021

Cancers

View full text Add to dashboard Cite

(1). Background: Immunohistochemical (IHC) evaluation of programmed death-1 (PD-1) and its ligand (PD-L1) is being used to evaluate advanced malignancies with potential response to immune checkpoint inhibitors. We evaluated both plasma and tissue expression of PD-1 and PD-L1 in the same cohort of patients, including non-metastatic and metastatic clear cell renal cell carcinoma (CCRCC). Concomitant plasma and tissue expression of PD-1 and PD-L1 was evaluated with emphasis on diagnostic and prognostic implications. (2) Methods: we analyzed PD-1 and PD-L1 IHC expression in tumor tissues and soluble forms (sPD-1 and sPD-L1) in plasma from 89 patients with CCRCC, of which 23 were metastatic and 16 received systemic therapy. The primary endpoint was evaluation of overall survival using Kaplan-Meier analysis and the Cox regression model. Plasma samples from healthy volunteers were also evaluated. (3) Results: Interestingly, sPD-1 and sPD-L1 levels were lower in cancer patients than in controls. sPD-1 and sPD-L1 levels and their counterpart tissue expression both at the tumor center and infiltrating front were not associated. Higher expression of both PD-1 and PD-L1 were associated with tumor grade, necrosis and tumor size. PD-1 was associated to tumor stage (pT) and PD-L1 to metastases. sPD-1 and sPD-L1 were not associated with clinico-pathological parameters, although both were higher in patients with synchronous metastases compared to metachronous ones and sPD-L1 was also higher for metastatic patients compared to non-metastatic patients. sPD-1 was also associated with the International Metastatic Renal Cell Cancer Database Consortium (IMDC) prognostic groups in metastatic CCRCC and also to the Morphology, Attenuation, Size and Structure (MASS) response criteria in metastatic patients treated with systemic therapy, mainly tyrosine-kinase inhibitors. Regarding prognosis, PD-L1 immunostaining at the tumor center with and without the tumor front was associated with worse survival, and so was sPD-L1 at a cut-off >793 ng/mL. Combination of positivity at both the tissue and plasma level increased the level of significance to predict prognosis. (4) Conclusions: Our findings corroborate the role of PD-L1 IHC to evaluate prognosis in CCRCC and present novel data on the usefulness of plasma sPD-L1 as a promising biomarker of survival in this neoplasia.

show abstract

Section: Discussionmentioning

confidence: 99%

Soluble PD-L1 Is an Independent Prognostic Factor in Clear Cell Renal Cell Carcinoma

Larrinaga

Solano-Iturri

Errarte

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…Still, immunohistochemical staining (not only in the case of PD-L1) in solid cancers can be influenced in a negative manner by various technical issues, including time length and type of tissue fixation, section preparation, and the quantity of tissue used (whole sections or tissue microarrays) presenting further challenges for reproducibility [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

PD-L1 Expression in Muscle Invasive Urothelial Carcinomas as Assessed via Immunohistochemistry: Correlations with Specific Clinical and Pathological Features, with Emphasis on Prognosis after Radical Cystectomy

Nechifor-Boilă

Loghin

Nechifor-Boilă

et al. 2021

Life

View full text Add to dashboard Cite

In the present study, we analyzed Programmed Death Ligand-1 (PD-L1) expression in radical cystectomy (RC) specimens from patients with muscle-invasive urothelial carcinoma (UC), in order to assess any correlations with specific clinicopathological features and its potential prognostic value. A multi-institutional study was performed within the departments of urology and pathology at the Mureș County Hospital, Romania, and Centre Hospitalier Lyon Sud, France. Sixty-nine patients with MIBC were included, for whom tumor histology (conventional versus histological variant/differentiation), tumor extension (T), lymph node involvement (N), and distant metastases (M) were recorded. PD-L1 immunostaining was performed using the 22C3 clone and was interpreted using the combined positive score (CPS) as recommended (Dako Agilent, Santa Clara, CA, USA). Positive PD-L1 immunostaining was more prevalent among UCs with squamous differentiation compared to conventional UCs and trended towards an improved OS (p = 0.366). We found the T stage to be a risk factor for poor survival in PD-L1-positive patients (HR 2.9, p = 0.021), along with the N stage in PD-L1-negative patients (HR 1.98, p = 0.007). No other clinicopathological factor was found to be significantly associated with PD-L1 positivity. Thus, we confirm the need for PD-L1 immunostaining prior to initiating immune checkpoint inhibitor therapy for a more accurate assessment of the patients’ chances of responding to treatment.

show abstract

“…PD-L1 expression on tumor cells predicts efficacy of PD-1/PD-L1 inhibitors in several tumor types. More recently, guidelines for implementation and interpretation of PD-L1 expression has been published [ 98 ]. However, the value of PD-L1 as the “definitive” biomarker is controversial [ 99 , 100 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical Trials of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Dyhl-Polk

Mikkelsen

Ladekarl

et al. 2021

JCM

View full text Add to dashboard Cite

Introduction: Several immune checkpoint inhibitors (CPIs) are under clinical development in hepatocellular carcinoma (HCC) and the field is advancing rapidly. In this comprehensive review, we discuss published results and report on ongoing clinical trials. Methods: A literature search was carried out using PubMed and EMBASE; data reported at international meetings and clinicaltrials.gov were included as well. The search was updated 5 March 2021. We evaluated studies with monotherapy CPI’s, combinations of CPI’s and combinations of CPI’s with other treatment modalities separately. Only studies with at least 10 included patients were considered. Results: We identified 2649 records published in the English language literature. After review, 29 studies remained, including 12 studies with preliminary data only. The obtained overall response rate of PD-1/PDL-1 monotherapy in phase II studies in the second-line setting was 15–20% with disease control in approximately 60% of patients. The responses were of long duration in a subset of patients. Furthermore, the safety profiles were manageable. However, a phase III study comparing nivolumab with sorafenib in the first-line setting and a phase III study evaluating pembrolizumab versus best supportive care in the second-line setting did not meet their prespecified endpoints. More recently, a phase I/II study of nivolumab and ipilimumab has resulted in a response rate of approximately 30% with a median OS of 22 months in the second-line setting. Multiple trials have been initiated to evaluate CPIs in combination with molecularly targeted drugs, especially anti-angiogenic drugs or local therapy. A phase III study investigating atezolizumab plus bevacizumab versus sorafenib in the first-line setting showed significantly increased survival in the combination arm. Conclusions: The combination of atezolizumab and bevacizumab represents a new standard of care in the first-line setting for fit patients with preserved liver function. CPIs can produce durable tumor remission and induce long-standing anti-tumor immunity in a subgroup of patients with advanced HCC. Although phase III trials of CPI monotherapy have been negative, the combination of PD-1/PD-L1 inhibitors with other anti-angiogenic drugs, CTLA-4 inhibitors or other modalities may result in new treatment options for patients with HCC. Research on predictive biomarkers is crucial for further development of CPIs in HCC.

show abstract

Programmed death ligand-1 (PD-L1) as a predictive marker for immunotherapy in solid tumours: a guide to immunohistochemistry implementation and interpretation

Cited by 140 publications

References 105 publications

Soluble PD-L1 Is an Independent Prognostic Factor in Clear Cell Renal Cell Carcinoma

Soluble PD-L1 Is an Independent Prognostic Factor in Clear Cell Renal Cell Carcinoma

PD-L1 Expression in Muscle Invasive Urothelial Carcinomas as Assessed via Immunohistochemistry: Correlations with Specific Clinical and Pathological Features, with Emphasis on Prognosis after Radical Cystectomy

Clinical Trials of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Contact Info

Product

Resources

About