Results from a Meta-analysis of Combination of PD-1/PD-L1 and CTLA-4 Inhibitors in Malignant Cancer Patients: Does PD-L1 Matter?

Feng, Yuqian; Jin, Han Seung; Guo, Kaibo; Xiang, Yuying; Zhang, Yiting; Du, Wurong; Shen, Minhe; Ruan, Shanming

doi:10.3389/fphar.2021.572845

Cited by 7 publications

(8 citation statements)

References 41 publications

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“…During the last few years, cancer immunotherapy has demonstrated promising results with different types of tumors [9][10][11][12]. In particular, with the introduction of immune checkpoint inhibitor (ICI)-targeted immunotherapy, the immunotolerant tumor microenvironment can be overcome by reactivating T cells, enhancing anti-tumor immunity, and eliminating tumor cells more effectively [13].…”

Section: Introductionmentioning

confidence: 99%

PD-L1/PD-1 and CTLA-4 Expression in Equine Penile Squamous Cell Carcinomas

Porcellato

Mecocci

Brachelente

et al. 2021

Animals

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In horses, penile squamous cell carcinomas (epSCCs) are among the most common cutaneous neoplastic lesions. These tumors usually arise in benign lesions such as viral plaques and papillomas frequently induced by Equus caballus papillomavirus type 2 (EcPV2) infection. In the last decade, the introduction of immune checkpoint inhibitors (ICI) for the treatment of human cancers has demonstrated promising results. Among the most commonly targeted pathways, there is PD-1/PD-L1 and CTLA-4. The aim of this study is to investigate the expression of the PD-1/PD-L1 pathway and CTLA-4 in the tumor microenvironment of epSCCs to assess the feasibility of an immunotherapeutic approach. Twenty equine epithelial tumors were retrospectively selected and submitted to RT-qPCR for PD-1 and PD-L1 genes. After testing antibodies cross-reactivity by western blotting, immunohistochemistry for PD-L1 and CTLA-4 was performed. Results from RT-qPCR demonstrated that 3/20 cases expressed the PD-L1 gene, whereas the PD-1 gene was not detected. Immunohistochemical positivity for PD-L1 was found only in one case. CTLA-4-positive cells were observe in all cases but were few (Mdn = 4.8; IQR = 2.3–7.1 cells/HPF). In this study group, PD-1/PD-L1 and CTLA-4 do not appear to be highly expressed and therefore the use of ICI in epSCCs may not have promising rates of response.

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Section: Introductionmentioning

confidence: 99%

PD-L1/PD-1 and CTLA-4 Expression in Equine Penile Squamous Cell Carcinomas

Porcellato

Mecocci

Brachelente

et al. 2021

Animals

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“…Results were correlated with clinicopathological data and the study reveals worse OS in case of high expression levels of PD-L1 and a higher risk of developing neck node metastases, indicating that CPI may be appropriate even in early tumor stage to prevent further disease progression ( 84 ). Feng et al ( 85 ) perform a meta-analysis of the combination of PD-1/PD-L1 and CTLA-4 inhibitors in patients with malignant tumors to address the significance of PD-L1. Notably, they find higher PD-L1 expression to be associated with longer PFS.…”

Section: Biomarkers For Immunotherapy In Head and Neck Cancermentioning

confidence: 99%

Biomarkers and 3D models predicting response to immune checkpoint blockade in head and neck cancer (Review)

et al. 2022

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Immunotherapy has evolved into a powerful tool in the fight against a number of types of cancer, including head and neck squamous cell carcinomas (HNSCC). Although checkpoint inhibition (CPI) has definitely enriched the treatment options for advanced stage HNSCC during the past decade, the percentage of patients responding to treatment is widely varying between 14-32% in second-line setting in recurrent or metastatic HNSCC with a sporadic durability. Clinical response and, consecutively, treatment success remain unpredictable in most of the cases. One potential factor is the expression of target molecules of the tumor allowing cancer cells to acquire therapy resistance mechanisms. Accordingly, analyzing and modeling the complexity of the tumor microenvironment (TME) is key to i) stratify subgroups of patients most likely to respond to CPI and ii) to define new combinatorial treatment regimens. Particularly in a heterogeneous disease such as HNSCC, thoroughly studying the interactions and crosstalking between tumor and TME cells is one of the biggest challenges. Sophisticated 3D models are therefore urgently needed to be able to validate such basic science hypotheses and to test novel immuno-oncologic treatment regimens in consideration of the individual biology of each tumor. The present review will first summarize recent findings on immunotherapy, predictive biomarkers, the role of the TME and signaling cascades eliciting during CPI. Second, it will highlight the significance of current promising approaches to establish HNSCC 3D models for new immunotherapies. The results are encouraging and indicate that data obtained from patient-specific tumors in a dish might be finally translated into personalized immuno-oncology.

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“…Combination therapy with anti-CTLA4 and anti-PD1/PDL1 has improved clinical outcomes in various solid tumors, supporting the synergistic effect of this combination. 47 …”

Section: First-line Systemic Therapeutic Optionsmentioning

confidence: 99%

Systemic Therapy in Advanced Hepatocellular Carcinoma: Patient Selection and Key Considerations

Storandt¹,

Mahipal²,

Tella³

et al. 2022

JHC

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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Most patients with HCC have advanced disease at initial diagnosis, and sorafenib has been the only systemic treatment option for more than a decade in patients with advanced, unresectable HCC. However, there has been a dramatic change in the treatment algorithm in the last several years, given new drug approvals in the field. Most importantly, the combination of atezolizumab and bevacizumab has demonstrated clinically meaningful benefits in terms of response rate, progression-free survival, and overall survival compared to sorafenib in the first-line setting. Recently a phase III trial showed that the combination of durvalumab with a single dose of tremelimumab improved overall survival compared to sorafenib, while durvalumab monotherapy was found to be noninferior to sorafenib, making it an attractive alternative single agent in selected patient populations. As immunotherapy makes its way into the therapeutic landscape of HCC, other novel targeted therapies, such as lenvatinib, cabozantinib, ramucirumab, and regorafenib, have also been approved by regulatory authorities for treatment of advanced, unresectable HCC. This review article focuses on the first-line systemic treatment options for HCC while addressing some of the most important questions aimed at optimization of HCC treatment.

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Results from a Meta-analysis of Combination of PD-1/PD-L1 and CTLA-4 Inhibitors in Malignant Cancer Patients: Does PD-L1 Matter?

Cited by 7 publications

References 41 publications

PD-L1/PD-1 and CTLA-4 Expression in Equine Penile Squamous Cell Carcinomas

PD-L1/PD-1 and CTLA-4 Expression in Equine Penile Squamous Cell Carcinomas

Biomarkers and 3D models predicting response to immune checkpoint blockade in head and neck cancer (Review)

Systemic Therapy in Advanced Hepatocellular Carcinoma: Patient Selection and Key Considerations

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