Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The challenge to improve the clinical efficacy and enlarge the population that benefits from immune checkpoint inhibitors (ICIs) for non-small-cell lung cancer (NSCLC) is significant. Based on whole-exosome sequencing analysis of biopsies from NSCLC patients before anti-programmed cell death protein-2 (PD-1) treatment, we identified NLRP4 mutations in the responders with a longer progression-free survival (PFS). Knockdown of NLRP4 in mouse Lewis lung cancer cell line enhanced interferon (IFN)-α/β production through the cGAS-STING-IRF3/IRF7 axis and promoted the accumulation of intratumoral CD8 T cells, leading to tumor growth retardation in vivo and a synergistic effect with anti-PD-ligand 1 therapy. This was consistent with clinical observations that more tumor-infiltrating CD8 T cells and elevated peripheral IFN-α before receiving nivolumab treatment were associated with a longer PFS in NSCLC patients. Our study highlights the roles of tumor-intrinsic NLRP4 in remodeling the immune contextures in the tumor microenvironment, making regional type I IFN beneficial for ICI treatment.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8898729 | PMC |
| http://dx.doi.org/10.1111/cas.15243 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Choosing the best first-line therapy for extensive-stage small-cell lung cancer: anti-PD-1 or anti-PD-L1 inhibitors?
Medicine (Baltimore)
September 2025
Department of Radiotherapy, Shaoxing Second Hospital, Shaoxing, Zhejiang, China.
Background: This study addresses the lack of a comprehensive meta-analysis comparing the efficacy and safety of first-line anti-blocking the programmed cell death 1 (PD-1) and anti-programmed death ligand 1 (PD-L1) therapies in patients with extensive-stage small-cell lung cancer, using reconstructed individual patient data.
Methods: Through systematic review, we extracted relevant studies from PubMed and EMBASE databases, spanning January 1, 2010 to November 28, 2024. Only phase III randomized controlled trials assessing anti-PD-1 inhibitors plus chemotherapy (CT) versus anti-PD-L1 inhibitors plus CT were selected.
Randomized clinical efficacy and safety study of peltopepimut-S plus cemiplimab compared to cemiplimab alone in patients with recurrent/metastatic HPV16-positive head and neck cancer.
J Immunother Cancer
September 2025
The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Background: Peltopepimut-S is a therapeutic vaccine, which induces specific expansion of both CD4+helper and CD8+cytotoxic T-cells against human papillomavirus type 16 (HPV16) E6/E7 oncoproteins.
Patients And Methods: In a randomized phase 2 trial, we evaluated the efficacy and safety of peltopepimut-S plus cemiplimab compared with cemiplimab alone as first-line or second-line therapy in recurrent/metastatic HPV16-positive head and neck cancer. The primary efficacy endpoint was the objective response rate (ORR) by an independent review (Response Evaluation Criteria in Solid Tumors version 1.
Prognosis and Toxicity Stratified by Best Tumor Burden Change in Japanese Patients With Advanced Melanoma Treated With First-Line Programmed Cell Death Protein 1 Monotherapy.
J Dermatol
September 2025
Department of Dermatology, Shizuoka Cancer Center, Shizuoka, Japan.
Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in patients with advanced malignant melanoma (MM). However, more than half of patients receiving anti-programmed cell death protein-1 (PD-1) antibody monotherapy still fail to respond, with response rates varying by race and melanoma subtype. Additionally, immune-related adverse events (irAEs) remain a major concern.
View Article and Find Full Text PDFAchieving an Objective Response Following Two Cycles of Neoadjuvant Chemotherapy Plus Anti-PD-(L)1 Inhibitors Might Predict the Optimal Pathological Response in Resectable Stage II-III Nonsmall Cell Lung Cancer.
Clin Lung Cancer
August 2025
Department of Thoracic Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi'an, Shaanxi, China. Electronic address:
Background: Neoadjuvant chemotherapy plus anti-programmed death (ligand)-1 (anti-PD-(L)1) inhibitors (chemoimmunotherapy) for early-stage nonsmall cell lung cancer (NSCLC) is under investigation, but differences in pathological response rates between patients who achieved objective responses after 2 versus 3-6 cycles remain unclear.
Methods: We retrospectively enrolled 481 stage II-III NSCLC patients who had 2-6 cycles of neoadjuvant chemoimmunotherapy followed by surgery (June 2018-February 2024). The primary outcomes compared the pathological response (pathological complete response [pCR] and major pathological response [MPR]) between the 2-cycle (n = 99) and 3-6-cycle (n = 382) groups in patients who achieved objective response as well as between objective response rate (ORR) and non-ORR groups.
Development of combinatorial immunotherapy for patients with advanced gastric cancer from the perspective of immunosuppressive mechanisms in the tumor microenvironment.
Fukushima J Med Sci
September 2025
Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine.
Combinatorial immunotherapy using anti-programmed cell death 1 (PD-1) monoclonal antibody (mAb) is being developed to overcome the limited efficacy of monotherapy with anti-PD-1 mAb for patients with advanced gastric cancer (GC). Anti-PD-1 mAb exhibits clinical efficacy by enhancing the function of cytotoxic T lymphocyte (CTL) through the inhibition of the PD-1 pathway;however, there are various immunosuppressive mechanisms that inhibit CTL function, as well as the PD-1 pathway in the tumor microenvironment (TME). Immune suppressive cells and expression of the inhibitory immune checkpoint molecules are included as main inhibitory mechanisms against CTL in the TME.
View Article and Find Full Text PDF