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| http://dx.doi.org/10.1016/j.cgh.2021.05.001 | DOI Listing |
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Durvalumab and tremelimumab in patients with advanced rare cancer: a multi-centre, non-blinded, open-label phase II basket trial.
EClinicalMedicine
January 2025
Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada.
Background: Dual inhibition of cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed death ligand 1 (PD-L1) has been shown to be an effective treatment strategy in many cancers. We sought to determine the objective response rate of combination durvalumab (D) plus tremelimumab (TM) in parallel cohorts of patients with carefully selected rare cancer types in which these agents had not previously been evaluated in phase II trials and for which there was clinical or biological rationale for dual immune checkpoint inhibitor therapy to be active.
Methods: We designed a multi-centre, non-blinded, open-label phase II basket trial with each of the following 8 rare cancers considered a separate phase II trial: salivary carcinoma, carcinoma of unknown primary (CUP) with tumour infiltrating lymphocytes and/or expressing PD-L1, mucosal melanoma, acral melanoma, osteosarcoma, undifferentiated pleomorphic sarcoma, clear cell carcinoma of the ovary (CCCO) or squamous cell carcinoma of the anal canal (SCCA).
A mechanistic, functional, and clinical perspective on targeting CD70 in cancer.
Cancer Lett
December 2024
Department of Surgery, Division of Surgical Oncology, College of Medicine, University of Illinois Chicago, Chicago, IL, 60612, USA; University of Illinois Hospital and Health Sciences System Cancer Center, University of Illinois Chicago, Chicago, IL, 60612, USA; Research Unit, Jesse Brown VA Medical Center, Chicago, IL, 60612, USA. Electronic address:
The oncoimmunology research has witnessed notable advancements in recent years. Reshaping the tumor microenvironment (TME) approach is an effective method to improve antitumor immune response. The T cell-mediated antitumor response is crucial for favorable therapeutic outcomes in several cancers.
View Article and Find Full Text PDFThe immune checkpoint LAG-3 is expressed by melanoma cells and correlates with clinical progression of the melanoma.
Oncoimmunology
December 2025
Heidelberg University, Medical Faculty Heidelberg, Department of Dermatology and National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and University Hospital Heidelberg, Heidelberg, Germany.
Immune checkpoint blockers have substantially improved prognosis of melanoma patients, nevertheless, resistance remains a significant problem. Here, intrinsic and extrinsic factors in the tumor microenvironment are discussed, including the expression of alternative immune checkpoints such as lymphocyte activation gene 3 (LAG-3) and T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3). While most studies focus on immune cell expression of these proteins, we investigated their melanoma cell intrinsic expression by immunohistochemistry in melanoma metastases of 60 patients treated with anti-programmed cell death protein 1 (PD-1) and/or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapy, and correlated it with the expression of potential ligands, RNA sequencing data and clinical outcome.
View Article and Find Full Text PDFDiagnostic and predictive values of m5C‑associated genes in idiopathic pulmonary fibrosis.
Mol Med Rep
February 2025
Department of Pulmonary and Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.
In patients with idiopathic pulmonary fibrosis (IPF), the role of 5‑methylcytosine (m5C)‑associated genes in the pathogenesis and development of the disease remains unclear. The present study aimed to identify reliable diagnostic markers based on the expression of m5C‑associated genes for the early detection of IPF. Count data were obtained by screening the IPF genome‑wide assay in the Gene Expression Omnibus database, followed by a comparison of m5C gene expression in patients with IPF and controls.
View Article and Find Full Text PDFEfficacy of CTLA-4 checkpoint therapy is dependent on IL-21 signaling to mediate cytotoxic reprogramming of PD-1CD8 T cells.
Nat Immunol
December 2024
Faculty of Medicine, Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology and Infectious Disease, University Medical Center Freiburg, Freiburg, Germany.
The mechanisms underlying the efficacy of anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) therapy are incompletely understood. Here, by immune profiling responding PD-1CD8 T (T) cell populations from patients with advanced melanoma, we identified differential programming of T cells in response to combination therapy, from an exhausted toward a more cytotoxic effector program. This effect does not occur with anti-PD-1 monotherapy.
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