Background: The immune landscape of uveal melanoma liver metastases (UMLM) has not been sufficiently studied.
Methods: Immune cell infiltrates (ICIs), PD-1 and PD-L1 were characterised in 62 UMLM and 28 primary uveal melanomas (PUM). ICI, PD-1 and PD-L1 were scored as: (1) % tumoral area occupied by tumour-infiltrating lymphocytes or macrophages (TILs, TIMs) and (2) % perTumoral (perT) area. ICIs and other variables including histopathologic growth patterns (HGPs), replacement and desmoplastic, of UMLM were analysed for their prognostic value.
Results: ICIs recognised by haematoxylin-eosin-saffron (HES) and IHC (e.g., T cells (CD3), B cells (CD20). Macrophages (CD68), (CD163), were primarily localised to the perT region in PUM and UMLM and were more conspicuous in UMLM. HES, CD3, CD4, FoxP3, CD8, CD20, PD-1 TILs were scant (<5%). TIMs were more frequent, particularly in UMLM than in PUM. Both CD68+ TIMs and HGPs remained significant on multivariate analysis, influencing overall (OS) and metastasis-specific overall survival (MSOS). CD68 + , CD163+ and CD20+ perT infiltrates in UMLM predicted increased OS and MSOS on univariate analysis.
Conclusions: TILs and PD-L1 have no predictive value in PUM or UMLM. CD68+ and CD163+TIMs, CD20+ perT lymphocytes, and HGPs are important prognostic factors in UMLMs.
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http://dx.doi.org/10.1038/s41416-023-02331-w | DOI Listing |
Exp Cell Res
December 2024
Medical Laboratory Technique College, The Islamic University, Najaf, Iraq; Medical Laboratory Technique College, The Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq; Medical Laboratory Technique College, The Islamic University of Babylon, Babylon, Iraq. Electronic address:
Exosomes are membrane-bound vesicles secreted by diverse cell types, serving as crucial mediators in intercellular communication and significantly influencing cancer development. Exosomes facilitate complex signaling processes in the tumor microenvironment for immunomodulation, metastasis, angiogenesis, and treatment resistance. Notably, long non-coding RNAs (lncRNAs), a class of non-coding RNAs, engage with mRNA, DNA, proteins, and miRNAs to modulate gene expression through multiple mechanisms, including transcriptional, post-transcriptional, translational, and epigenetic pathways.
View Article and Find Full Text PDFLung Cancer
December 2024
Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Electronics, Information and Bioengineering, Polytechnic University of Milan, Milan, Italy.
Introduction: KRAS mutation the most common molecular alteration in advanced non-small cell lung cancer (NSCLC) and is associated with an unfavourable prognosis, largely due to the lack of targeted therapeutic options for the majority of the KRAS mutated isoforms. The landscape of NSCLC treatment has expanded with the introduction of immune checkpoint inhibitors (ICIs). Nonetheless, data regarding the efficacy of ICI in NSCLC patients harbouring KRAS mutations are conflicting.
View Article and Find Full Text PDFBr J Dermatol
December 2024
Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Background: The tumour microenvironment significantly influences the clinical response of patients to therapeutic immune checkpoint inhibition (ICI), but a comprehensive understanding of the underlying immune-regulatory proteome is still lacking.
Objectives: To decipher targetable biologic processes that determine tumour-infiltrating lymphocytes (TiLs) as a cellular equivalent of clinical response to ICI.
Methods: We mapped the spatial distribution of proteins in TiL-enriched vs.
BioDrugs
December 2024
Rheumatology Department, Strasbourg University Hospital, 1 Avenue Molière, 67000, Strasbourg, France.
Chimeric antigen receptor (CAR) T-cell therapy, initially successful in treating hematological malignancies, is emerging as a potential treatment for autoimmune diseases, including rheumatic conditions. CAR T cells, engineered to target and eliminate autoreactive B cells, offer a novel approach to managing diseases like systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and inflammatory myopathies, where B cells play a pivotal role in disease pathology. Early case reports have demonstrated promising results, with patients achieving significant disease remission, normalization of serological markers, and the ability to discontinue traditional immunosuppressive therapies, which supported the initiation of several clinical trials.
View Article and Find Full Text PDFJ Neurooncol
December 2024
Department of Neurosurgery, Warren Alpert Medical School of Brown University, 222 Richmond St, Providence, RI, 02903, USA.
Purpose: Chordoma, a rare malignancy of the axial skeleton and skull base, presents significant therapeutic challenges due to the high rates of tumor recurrence and resistance. While surgical resection and radiation therapy remain the gold standard of treatment, the lack of additional treatment options necessitates the exploration of novel therapies. Combinatorial therapies hold significant potential in shaping patient prognosis.
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