Review
Immunology
Qian Li, Jingjing Han, Yonglin Yang, Yu Chen
Summary: Hepatocellular carcinoma (HCC) has a high prevalence and mortality rate worldwide. In recent years, immunotherapy using immune checkpoint inhibitors, particularly targeting the PD-1/PD-L1 axis, has brought fundamental changes to the treatment of advanced HCC. However, challenges remain and combination therapy may be a better option to improve the low remission rate.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Quanqing Tang, Shihao Li, Gaozhen Huang, Hongwei Liu
Summary: Urothelial carcinoma (UC) is a common malignant tumor. Platinum-based chemotherapy has been the standard treatment for metastatic UC, but immune checkpoint inhibitors (ICIs) offer hope for patients unfit for platinum therapy.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jun Wan, Hongji Dai, Xiaoli Zhang, Sheng Liu, Yuan Lin, Ally-Khan Somani, Jingwu Xie, Jiali Han
Summary: The majority of non-melanoma skin cancer cases are basal cell carcinoma and squamous cell carcinoma which originate from keratinocytes. The incidence of keratinocyte carcinomas in the US is over 5 million per year, three times higher than all other types of cancer combined. Research has shown significant variations in gene expression in these tumors, with novel findings including up-regulation of zinc finger encoding genes in human BCC and a novel link between hedgehog signaling, Wnt signaling, and the cilium.
Review
Nutrition & Dietetics
Yuqian Wang, Lingeng Lu, Changquan Ling, Ping Zhang, Rui Han
Summary: This study proposes a novel therapeutic strategy for breast cancer treatment by combining a diet containing HDAC2 inhibitors with PD-1/PD-L1 inhibitors, offering promising possibilities for improving treatment outcomes.
Article
Multidisciplinary Sciences
Changsheng Huang, Shengxiang Ren, Yaqi Chen, Anyi Liu, Qi Wu, Tao Jiang, Panjing Lv, Da Song, Fuqing Hu, Jingqing Lan, Li Sun, Xue Zheng, Xuelai Luo, Qian Chu, Keyi Jia, Yan Li, Jun Wang, Caicun Zou, Junbo Hu, Guihua Wang
Summary: This research discovered that PD-L1 K162 was methylated by SETD7 and demethylated by LSD2. Additionally, PD-L1 K162 methylation controlled the PD1/PD-L1 interaction and significantly enhanced the suppression of T cell activity in controlling cancer immune surveillance. The study demonstrated that PD-L1 hypermethylation was the key mechanism for anti-PD-L1 therapy resistance, identified PD-L1 K162 methylation as a negative predictive marker for anti-PD-1 treatment in patients with non-small cell lung cancer, and showed that the PD-L1 K162 methylation:PD-L1 ratio was a more accurate biomarker for predicting anti-PD-(L)1 therapy sensitivity.
Review
Oncology
Seri Jeong, Nuri Lee, Min-Jeong Park, Kibum Jeon, Wonkeun Song
Summary: This study reviewed laboratory techniques for detecting the PD-1 axis in metastatic breast cancer patients undergoing immunotherapy and highlighted the impact of variations in assay methods on result interpretation and clinical utility. The development of new methodologies for assessing PD-L1 expression and soluble PD-L1 has provided more accessible and non-invasive options for monitoring immune checkpoint levels in patients.
Review
Pharmacology & Pharmacy
Jinhua Liu, Zichao Chen, Yaqun Li, Wenjie Zhao, JiBiao Wu, Zhen Zhang
Summary: Programmed death protein 1 (PD1) is an important immune checkpoint on T cells that plays a crucial role in downregulating the immune system and promoting self-tolerance, while its ligand, programmed cell death ligand 1 (PDL1), is overexpressed in malignant tumor cells, contributing to immune evasion and treatment failure. Despite the clinical efficacy of PD1/PDL1 inhibitors in many tumors, some patients may develop drug resistance, highlighting the need for further research into improving targeted therapies and understanding the associated safety issues.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Ashray Maniar, Alyson Haslam, Vinay Prasad
Summary: Many control-arm patients in first-line trials did not receive PDI with established efficacy, highlighting the need for standardized approach to disease progression for these patients.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Oncology
Nicolai Gronne Jorgensen, Jeanette Kaae, Jacob Handlos Grauslund, Oezcan Met, Signe Ledou Nielsen, Ayako Wakatsuki Pedersen, Inge Marie Svane, Eva Ehrnrooth, Mads Hald Andersen, Claus Zachariae, Lone Skov
Summary: A study on the effect of the peptide vaccine IO103 in patients with basal cell carcinoma showed regression in tumor size in some cases, indicating potential effectiveness of the vaccine. Immune responses to the vaccine were observed in the majority of patients, suggesting a promising outcome.
Article
Oncology
Alexander Stein, Donjete Simnica, Christoph Schultheiss, Rebekka Scholz, Joseph Tintelnot, Eray Goekkurt, Lisa von Wenserski, Edith Willscher, Lisa Paschold, Markus Sauer, Sylvie Lorenzen, Jorge Riera-Knorrenschild, Reinhard Depenbusch, Thomas J. Ettrich, Steffen Doerfel, Salah-Eddin Al-Batran, Meinolf Karthaus, Uwe Pelzer, Lisa Waberer, Axel Hinke, Marcus Bauer, Chiara Massa, Barbara Seliger, Claudia Wickenhauser, Carsten Bokemeyer, Susanna Hegewisch-Becker, Mascha Binder
Summary: In MSS mCRC patients, immune checkpoint blockade is ineffective, but combining avelumab with standard treatment appears safe and feasible. PD-L1 mutations mediate subclonal immune escape to avelumab, particularly in patients expressing high-affinity Fc gamma R3a, leading to enhanced T cell killing and limiting subclonal expansion. Further trials evaluating the addition of avelumab in this patient subgroup are warranted.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Ewa Surmiak, Katarzyna Magiera-Mularz, Bogdan Musielak, Damian Muszak, Justyna Kocik-Krol, Radoslaw Kitel, Jacek Plewka, Tad A. Holak, Lukasz Skalniak
Summary: This article compares representative molecules from different classes in terms of their PD-1/PD-L1 dissociation capacity and in vitro bioactivity. Recent discoveries underscore important differences in the mechanisms of action of these molecules, with one principal feature to consider being the eventual human PD-L1 specificity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Tianyu Wang, Shi Cai, Yao Cheng, Wanheng Zhang, Minmin Wang, Huiyong Sun, Binghua Guo, Zheng Li, Yibei Xiao, Sheng Jiang
Summary: Compound 17 is a bifunctional inhibitor that can block the interactions between PD-1 and PD-L1, promoting internalization and degradation of PD-L1. It effectively suppresses tumor growth in vivo by activating antitumor immunity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Oncology
Douglas R. Adkins, Robert I. Haddad
Summary: PD-1 therapy has shown clinical activity in RM-NPC, with significant improvements in PFS observed in first-line setting trials. Whether combination chemoimmunotherapy or sequential chemotherapy followed by immunotherapy is more effective remains uncertain.
CANCER TREATMENT REVIEWS
(2022)
Article
Pharmacology & Pharmacy
Chengliang Sun, Yao Cheng, Xiaojia Liu, Gefei Wang, Wenjian Min, Xiao Wang, Kai Yuan, Yi Hou, Jiaxing Li, Haolin Zhang, Haojie Dong, Liping Wang, Chenguang Lou, Yanze Sun, Xinmiao Yu, Hongbin Deng, Yibei Xiao, Peng Yang
Summary: Programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) have emerged as promising immune checkpoint targets for cancer immunotherapy. This study focuses on the development of small-molecule inhibitors with improved binding capacity to PD-L1 protein. A novel phthalimide derivative, P39, was identified as the best inhibitor, which not only inhibited PD-1/PD-L1 interaction but also enhanced the killing efficacy of immune cells on cancer cells. P39 exhibited favorable safety profiles and showed significant in vivo antitumor activity through promoting CD8+ T cell activation.
ACTA PHARMACEUTICA SINICA B
(2022)
Review
Medicine, General & Internal
Donatella Gambini, Emanuela Passoni, Gianluca Nazzaro, Giada Beltramini, Gianluca Tomasello, Michele Ghidini, Elisabetta Kuhn, Ornella Garrone
Summary: Basal cell carcinoma (BCC) is a common form of skin cancer that primarily affects elderly patients but can also occur in younger individuals, especially those who are immunocompromised or genetically predisposed. Recent studies have shown a link between BCC development, the Hedgehog (Hh) signaling pathway, and the immune system, specifically in response to Hh pathway inhibitors like vismodegib and sonidegib.
FRONTIERS IN MEDICINE
(2022)