Clinical benefit of PD-1/PD-L1 inhibitors for poor performance status patients with advanced non-small cell lung cancerKoyama, Morise, Tanaka
et alJ Chemother (2025)
Abstract: The benefit of programmed cell death protein-1 (PD-1)/programmed cell death protein ligand-1 (PD-L1) inhibitors remains unclear in non-small cell lung cancer (NSCLC) patients with poor performance status (PS). In the current multi-centre retrospective cohort study, advanced or recurrent NSCLC patients treated with PD-1/PD-L1 inhibitors were enrolled. Of the 219 patients enrolled, 44 had PS 2-4. The objective response rate (ORR) of patients with PS 2-4 in 1st line was 33%. Among 1st line group, median progression-free survival (PFS) in patients with PS 2 was significantly longer compared to that in patients with PS 3-4 (15.3 months vs. 0.9 months, P = 0.039, Log-rank test). Among previously treated patients, the ORR of patients with PS 2-4 was only 4%, and PFS and overall survival was poor even in patients with PS 2. PD-1/PD-L1 inhibitors can be an option for PS 2 NSCLC patients in 1st line setting.
Immunologic correlates in a CIC::DUX4 fusion-positive sarcoma responsive to dual immune checkpoint blockadeBabatunde, Coca Membribes, Anthonescu
et alNPJ Precis Oncol (2025) 9 (1), 85
Abstract: CIC::DUX4 sarcoma (CDS) is a rare and aggressive subtype of soft tissue sarcoma with poor prognosis and limited treatment options. Immunotherapy has not been studied in this disease. To our knowledge, response to immune checkpoint blockade (ICB) has not been previously reported. Here, we present the first case of a patient with CDS responding to dual ICB with nivolumab and relatlimab. Immunohistochemical (IHC) analysis of pre-treatment samples revealed minimal immune cell infiltration, with scarce CD3+, CD8+, and FOXP3+ T-cells and negligible expression of PD-L1 and PD-1 markers. Post-treatment tumor samples revealed a significant shift in the immune microenvironment, with increased CD8 + T-cell infiltration and co-expression of exhaustion markers PD-1 and LAG-3 following treatment. These findings suggest that doublet ICB can activate an antitumor immune response in CDS, overcoming the immune cold phenotype typically associated with this sarcoma. This case provides the first evidence of dual PD-1/LAG-3 blockade inducing an immune response in CDS. The favorable response and tolerability observed in this patient highlight the potential of dual ICB as a therapeutic option in CDS that merits further investigation.© 2025. The Author(s).
Pancreatic Cancer Precursor Lesions - Can Immunotherapy Prevent Progression into Pancreatic Ductal Adenocarcinoma?Enzler, Frankel
Cancer Lett (2025)
Abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with a 5-year survival rate of only 12.5%. Early detection of PDAC or addressing risk factors for PDAC development are ways to improve outcomes. PDAC can arise from precursor lesions, including pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), and less frequent, mucinous cystic neoplasm (MCN), and other rare precursor variants. High-risk precursor lesions harbor a substantial chance of evolving into PDAC. Such lesions can often be found in resected PDAC specimens adjacent to the cancer. Unfortunately, recognizing precursor lesions that need to be resected is often tricky, and resections frequently end in major surgical interventions. Thus, better ways to handle precursor lesions are desperately needed. We mapped the immune microenvironments (IMEs) of PanINs, IPMNs, and MCNs on a cellular level using multiplex immunofluorescence and computational imaging technology and compared the findings to PDACs and normal pancreatic tissues. We found distinct and potentially targetable mechanisms of immunosuppression between the two main precursor lesions, PanIN and IMPN. Immunosuppression in IPMNs seems partly mediated by programmed cell death protein 1 ligand (PD-L1) expression on antigen-presenting cells (APCs). By contrast, elevated numbers of regulatory T cells (Tregs) seem to be key players in the immunosuppression of PanINs. Thus, treating high-risk IPMNs with anti-PD-1 and high-risk PanINs with agents targeting Tregs, such as anti-lymphocyte associated protein 4 (anti-CTLA-4) antibodies, could reverse their immunosuppressive state. Reversal of immunosuppression will restore immunosurveillance and eventually prevent progression into PDAC. We also review relevant published and ongoing non-surgical treatment approaches for high-risk IPMNs and PanINs.Copyright © 2025. Published by Elsevier B.V.
Immune checkpoint inhibitor-associated linear IgA bullous dermatosis with recalcitrant ocular involvement: a rare presentationSaeed, Hosking, Grando
Skin Health Dis (2025) 5 (1), 53-55
Abstract: Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) receptor inhibitors have become imperative in the treatment of advanced solid organ malignancies such as metastatic melanoma. With this disinhibition of certain immune responses to induce an antitumour response, numerous adverse events have been reported, many of which affect the skin. While rare, PD-1/PD-L1 inhibitor-associated severe cutaneous adverse reactions (SCARs) can cause significant morbidity and/or mortality. New SCARs are reported with increasing frequency as immune checkpoint inhibitors become more widely used. Here, we present a rare case of recalcitrant ocular linear IgA bullous dermatosis associated with a PD-1 inhibitor. Awareness of this entity will allow more rapid recognition and initiation of appropriate management and treatment, which would reduce the morbidity and/or mortality associated with these serious adverse reactions.© The Author(s) 2025. Published by Oxford University Press on behalf of British Association of Dermatologists.
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