What are the specific DNA or RNA aptamers that have been discovered for targeting PD-L1 in cancer research?5 answersSpecific DNA or RNA aptamers targeting PD-L1 in cancer research include the HIF-1α inhibitor at translation level (HITT) long noncoding RNA (lncRNA), PD-L1 antagonistic DNA aptamer incorporated into a molecularly imprinted polymer layer (APD–PD-L1–MIPL), and the high-affinity immunomodulatory IM-TLR9:PD-L1-ASO antisense oligonucleotide (IM-T9P1-ASO). These aptamers have shown promising results in inhibiting the PD-1/PD-L1 interaction, enhancing antitumor immunity, and overcoming resistance to anti-PD-L1 therapy. Additionally, miRNA34a delivered via iron oxide magnetic nanoparticles (IONPs) has been utilized to downregulate PD-L1 expression in cancer cells, demonstrating a novel gene delivery method for cancer immunotherapy. These findings highlight the diverse strategies involving aptamers for targeting PD-L1 in cancer therapy.
What are the potential drawbacks of using PD-L1 in the treatment of melanoma?5 answersPD-L1 expression in melanoma has been used as a potential biomarker for predicting response to immune checkpoint blockade (ICB) therapy. However, there are potential drawbacks associated with using PD-L1 in the treatment of melanoma. One drawback is that PD-L1 expression is not consistently correlated with clinical outcomes in melanoma patients treated with ICB therapy. Another drawback is the heterogeneity of PD-L1 expression within tumors, which can lead to discordant results and challenges in accurately assessing PD-L1 status. Additionally, the use of different PD-L1 antibodies in immunohistochemistry assays can result in variations in staining properties, further complicating the interpretation of PD-L1 expression. These drawbacks highlight the need for further research and refinement in the use of PD-L1 as a biomarker in melanoma treatment.
What is PD-1, PD-L1?4 answersPD-1 (programmed cell death protein 1) and PD-L1 (programmed death-ligand 1) are immune checkpoint molecules that play a key role in immune regulation and homeostasis. PD-L1 is a transmembrane ligand for PD-1, which is a receptor that inhibits T-cell activity. The PD-L1/PD-1 axis has been successfully targeted in cancer immunotherapy to enhance antitumor immune responses. Tethering PD-L1 to the membrane restricts its ability to inhibit immune responses, and its plasma membrane density can be modulated by regulating its trafficking. PD-L1 also has functions independent of its role as a ligand for PD-1, and its residence in different intracellular compartments may contribute to the regulation of those activities. The PD-1/PD-L1 axis has been explored in fibrotic diseases, further highlighting its role in immune regulation and fibrosis. PD-L1 and PD-1 expression have been studied in rare lung tumors, providing insights into their potential role in immunotherapy for these tumors.
Is PD-L1 expressed despite anti-PD-1therapy ?5 answersPD-L1 expression can be observed despite anti-PD-1 therapy. Studies have shown that PD-L1 expression on tumor tissues, as assessed by immunohistochemistry, is an imperfect biomarker that only applies to a limited number of cancers. Many patients with PD-L1-negative tumors still respond to anti-PD-(L)1 immunotherapy. Additionally, PD-L1 expression can be affected by platinum-based chemotherapy, with some patients showing significant upregulation in PD-L1 expression at recurrence. It has also been found that the extent of PD-1/PD-L1 interaction can vary among patients and within tumors, and patients with a low extent of PD-1/PD-L1 interaction may have worse outcomes with anti-PD-1 therapy. Therefore, PD-L1 expression can be observed despite anti-PD-1 therapy, and the regulation and function of PD-L1 in tumors are still being studied to better understand its role as a biomarker and potential therapeutic target.
Do PD-L1 scores above 50% further predict outcomes in patients with NSCLC?5 answersPD-L1 scores above 50% do not consistently predict outcomes in patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab. In a real-world Canadian population, only 21% of patients received second-line systemic therapy after single-agent pembrolizumab, despite second-line therapy being associated with prolonged survival. PD-L1 expression was found to be more predictive of benefit for patients with nonsquamous NSCLC than squamous NSCLC treated with immune checkpoint inhibitors (ICI). However, in patients with ALK-positive NSCLC treated with front-line alectinib, PD-L1 expression did not serve as a predictive biomarker for efficacy. In a cohort of patients with high PD-L1 expression NSCLC treated with first-line pembrolizumab, factors such as ECOG performance status, best response, and treatment beyond progression were associated with better outcomes, but PD-L1 expression alone did not consistently predict survival.
What is the most commonly used PD-L1 assay in China?4 answersThe most commonly used PD-L1 assay in China is immunohistochemistry (IHC) using tissue samples.