Inhibitory ligands on tumor cells and their corresponding receptors on T cells are collectively called immune checkpoint molecules and have emerged as druggable targets that harness endogenous immunity to fight cancer. Immune checkpoint inhibitors targeting CTLA-4, PD-1 and PD-L1 have been developed for the treatment of patients with non-small-cell lung cancer and other malignancies, with impressive clinical activity, durable responses and a favorable toxicity profile. This article reviews the development, current status and future directions for some of these agents. The efficacy and safety data for drugs such as ipilimumab, nivolumab, pembrolizumab, atezolizumab and durvalumab are reviewed, along with combination strategies and response evaluation criteria. The toxicity profiles and predictive biomarkers of response are also discussed.
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http://dx.doi.org/10.2217/fon.16.20 | DOI Listing |
Curr Cancer Drug Targets
January 2025
Division of Pharmacology, Guru Nanak Institute of Pharmaceutical Science and Technology, Kolkata, 700114, India.
Immune checkpoint blockade (ICB) has fundamentally transformed cancer treat-ment by unlocking the potency of CD8+ T cells by targeting the suppression of the CTLA-4 and PD-1/PD-L1 pathways. Nevertheless, ICBs are associated with the risk of severe side effects and resistance in certain patients, driving the search for novel and safer immune check-point modulators. Monoamine Oxidase A (MAO-A) plays an unexpected role in the field of cancer.
View Article and Find Full Text PDFCell Rep
January 2025
The Fourth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China; Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China. Electronic address:
CD8 T cell exhaustion (Tex) has been widely acknowledged in human cancer, while the underlying mechanisms remain unclear. Here, we demonstrate that reduced amino acid (aa) metabolism and mTOR inactivation are accountable for Tex in human non-small cell lung cancer (NSCLC). NSCLC cells impede the T cell-intrinsic transcription of SLC7A5 and SLC38A1, disrupting aa transport and consequently leading to mTOR inactivation.
View Article and Find Full Text PDFClin Transl Med
January 2025
Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Background: Immunotherapy is beneficial for some colorectal cancer (CRC) patients, but immunosuppressive networks limit its effectiveness. Cancer-associatedfibroblasts (CAFs) are significant in immune escape and resistance toimmunotherapy, emphasizing the urgent need for new treatment strategies.
Methods: Flow cytometric, Western blotting, proteomics analysis, analysis of public database data, genetically modified cell line models, T cell coculture, crystal violetstaining, ELISA, metabonomic and clinical tumour samples were conducted to assess the role of EDEM3 in immune escape and itsmolecular mechanisms.
World J Surg Oncol
January 2025
Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, China.
Objective: This study aims to elucidate the therapeutic efficacy and safety of a taxane-based chemotherapy in combination with immune checkpoint inhibitors regimen in patients diagnosed with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
Methods: We retrospectively collected clinical data from 154 patients who received at least two cycles of PD-1 inhibitors in combination with a taxane-based chemotherapy as first-line treatment in seven hospitals in Hunan Province, between December 2018 and December 2023. These patients were subjected to long-term follow-up.
Clin Epigenetics
January 2025
Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Background: The primary objective of this study was to examine whether ARID1A mutations confer a fitness advantage to gastric cancer from an immunological perspective, along with elucidating the underlying mechanism. Additionally, we aimed to identify the clinical potential of combining epigenetic inhibitors with immune checkpoint inhibitors to improve the efficacy of immunotherapy for gastric cancer.
Methods: The correlation between ARID1A gene expression and gastric cancer patient survival was analyzed using the GEO dataset GSE62254.
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