Anti-PD1/PD-L1 immunotherapy has emerged as a standard of care for stage III-IV non-small cell lung cancer (NSCLC) over the past decade. Patient selection is usually based on PD-L1 expression by tumor cells and/or tumor mutational burden. However, mutations in oncogenic drivers such as , , , or modify the immune tumor microenvironment and may promote anti-PD1/PD-L1 resistance. In this review, we discuss the molecular mechanisms associated with these mutations, which shape the immune tumor microenvironment and may impede anti-PD1/PD-L1 efficacy. We provide an overview of the current clinical data on anti-PD1/PD-L1 efficacy in NSCLC with oncogenic driver mutation.
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http://dx.doi.org/10.3390/ijms22126288 | DOI Listing |
Anticancer Res
December 2024
Department of Radiotherapy and Oncology, Democritus University of Thrace, Alexandroupolis, Greece;
Background/aim: The prognostic role of tissue PD-L1 expression in endometrial cancer (EC) remains controversial. Moreover, its value in guiding anti-PD1/PD-L1 immunotherapy is questionable. The eventual role of soluble PD-L1 (sPD-L1), released by cancer tissue and circulating immune cells, is largely unexplored.
View Article and Find Full Text PDFCurr Oncol
November 2024
Medical Oncology Department, University Hospital of Salamanca, 37007 Salamanca, Spain.
: Anti PD1/PD-L1 agents, including pembrolizumab, have revolutionized the oncological treatment of different types of cancer, including non-small cell lung cancer. The most frequent complications associated with this type of treatment are mild and are located at the thyroid, pulmonary or hepatic level. Sarcoid like reaction and mesenteric panniculitis secondary to pembrolizumab treatment are two very rare adverse effects.
View Article and Find Full Text PDFFront Pharmacol
June 2024
Institute for Breast Health Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, China.
Background: Although prognostic models based on pyroptosis-related genes (PRGs) have been constructed in bladder cancer (BLCA), the comprehensive impact of these genes on tumor microenvironment (TME) and immunotherapeutic response has yet to be investigated.
Methods: Based on expression profiles of 52 PRGs, we utilized the unsupervised clustering algorithm to identify PRGs subtypes and ssGSEA to quantify immune cells and hallmark pathways. Moreover, we screened feature genes of distinct PRGs subtypes and validated the associations with immune infiltrations in tissue using the multiplex immunofluorescence.
Int J Mol Sci
June 2024
Department of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
In oral squamous cell carcinoma (OSCC) tissues, an immunotolerant situation triggered by immune checkpoints (ICPs) can be observed. Immune checkpoint inhibitors (ICIs) against the PD1/PD-L axis are used with impressive success. However, the response rate is low and the development of acquired resistance to ICI treatment can be observed.
View Article and Find Full Text PDFBMC Cancer
June 2024
Translational and Clinical Research Institute, The Medical School, Newcastle University, William Leech Building, Framlington Place, Newcastle upon Tyne, NE4 2HH, UK.
Background: Checkpoint inhibitors (CPIs) are widely used in cancer treatment, with transformative impacts on survival. They nonetheless carry a significant risk of toxicity in the form of immune-related adverse events (IrAEs), which may be sustained and life-altering. IrAEs may require high-dose and/or prolonged steroid use and represent a significant healthcare burden.
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