98%
921
2 minutes
20
The discovery of immune checkpoints and the development of immune checkpoint inhibitors (ICI) have achieved a durable response in advanced-stage cancer patients. However, there is still a high proportion of patients who do not benefit from ICI therapy due to a lack of response when first treated (primary resistance) or detection of disease progression months after objective response is observed (acquired resistance). Here, we review the current FDA-approved ICI for the treatment of certain solid malignancies, evaluate the contrasting responses to checkpoint blockade in different cancer types, explore the known mechanisms associated with checkpoint blockade resistance (CBR), and assess current strategies in the field that seek to overcome these mechanisms. In order to improve current therapies and develop new ones, the immunotherapy field still has an unmet need in identifying other molecules that act as immune checkpoints, and uncovering other mechanisms that promote CBR.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10841019 | PMC |
http://dx.doi.org/10.1080/15384047.2024.2308097 | DOI Listing |
Nat Med
September 2025
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Immune checkpoint blockade (ICB) is standard of care in advanced diffuse pleural mesothelioma (DPM), but its role in the perioperative management of DPM is unclear. In tandem, circulating tumor DNA (ctDNA) ultra-sensitive residual disease detection has shown promise in providing a molecular readout of ICB efficacy across resectable cancers. This phase 2 trial investigated neoadjuvant nivolumab and nivolumab/ipilimumab in resectable DPM along with tumor-informed liquid biopsy residual disease assessments.
View Article and Find Full Text PDFPLoS Pathog
September 2025
School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
Zika virus (ZIKV) has emerged as a rising concern in global health in recent years. The role of PD-1/PD-L1 immune checkpoint in acute ZIKV infection remains to be understood. In this study we demonstrated the activation of PD-1/PD-L1 immune checkpoint by ZIKV.
View Article and Find Full Text PDFCancer Immunol Res
September 2025
University of Pennsylvania, Philadelphia, PA, United States.
Pancreatic ductal adenocarcinoma (PDA) is defined by a myeloid-enriched microenvironment and has shown remarkable resistance to immune checkpoint blockade (e.g., PD-1 and CTLA-4).
View Article and Find Full Text PDFACS Nano
September 2025
School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.
Although traditional immunogenic cell death (ICD) inducers generate vaccines (ISV) to potentiate antiprogrammed cell death ligand 1 (anti-PDL1) antibodies therapy, their efficacy remains limited. This limitation may be attributed to the physical barrier created by extracellular matrix (ECM) and immunosuppressive metabolic barrier mediated by adenosine. Here, we report an oncolytic polymer (OP), a well-designed ε-polylysine derivative with ICD-inducing capacity, which can simultaneously facilitate the release of endogenous ECM-degrading enzyme, Cathepsin B.
View Article and Find Full Text PDFCureus
August 2025
Department of Ophthalmology, Hôpital Maisonneuve-Rosemont, Montreal, CAN.
Choroidal metastasis from occult cutaneous melanoma is rare and can masquerade as ocular inflammation. A 70‑year‑old man with sectoral anterior scleritis was found on multimodal imaging to have a solitary choroidal mass with mild periscleral fluid, prompting systemic evaluation that uncovered colonic polyps that, on histopathology, contained metastatic melanoma, a scalp primary, and widespread visceral, nodal, and intracranial metastases. Tumour cells stained HMB‑45, Melan‑A, and SOX10 positive, AE1/AE3 negative, and carried an NRAS‑Q61 mutation with wild‑type BRAF, confirming cutaneous origin.
View Article and Find Full Text PDF