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Immune checkpoint blockade (ICB) therapies exhibit substantial clinical benefit in different cancers, but relatively low response rates in the majority of patients highlight the need to understand mutual relationships among immune features. Here, we reveal overall positive correlations among immune checkpoints and immune cell populations. Clinically, patients benefiting from ICB exhibited increases for both immune stimulatory and inhibitory features after initiation of therapy, suggesting that the activation of the immune microenvironment might serve as the biomarker to predict immune response. As proof-of-concept, we demonstrated that the immune activation score ( ) based on dynamic alteration of interleukins in patient plasma as early as two cycles (4-6 weeks) after starting immunotherapy can accurately predict immunotherapy efficacy. Our results reveal a systematic landscape of associations among immune features and provide a noninvasive, cost-effective, and time-efficient approach based on dynamic profiling of pre- and on-treatment plasma to predict immunotherapy efficacy.
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http://dx.doi.org/10.1016/j.xinn.2021.100194 | DOI Listing |
Immunol Res
September 2025
Department of Immunology and Allergy, Faculty of Medicine, Necmettin Erbakan University, Konya, Türkiye.
Background: Variants of uncertain significance (VUS) represent a major diagnostic challenge in the interpretation of genetic testing results, particularly in the context of inborn errors of immunity such as severe combined immunodeficiency (SCID). The inconsistency among computational prediction tools often necessitates expensive and time-consuming wet-lab analyses.
Objective: This study aimed to develop disease-specific, multi-class machine learning models using in silico scores to classify SCID-associated genetic variants and improve the interpretation of VUS.
J Immunother Cancer
September 2025
Harold C Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
Background: While highly efficacious for numerous cancers, immune checkpoint inhibitors (ICIs) can cause unpredictable and potentially severe immune-related adverse events (irAEs), underscoring the need to understand irAE biology.
Methods: We used a multidimensional approach incorporating single-cell RNA sequencing, mass cytometry, multiplex cytokine assay, and antinuclear antibody (ANA) profiling to characterize the peripheral immune landscape of patients receiving ICI therapy according to irAE development.
Results: Analysis of 162 patients revealed that individuals who developed clinically significant irAEs exhibited a baseline proinflammatory, autoimmune-like state characterized by a significantly higher abundance of CD57 T and natural killer (NK) T cells, plasmablasts, proliferating and activated CXCR3 lymphocytes, CD8 effector and terminal effector memory T cells, along with reduced NK cells and elevated plasma ANA levels.
J Immunother Cancer
September 2025
Division of Hematology & Oncology, Department of Medicine, School of Medicine, University of California, Irvine, California, USA
Background: γδ T cells possess unique immunological features including tissue tropism, major histocompatibility complex-independent antigen recognition, and hybrid T/natural killer cell properties that make them promising candidates for cancer immunotherapy. However, the therapeutic potential of Vδ1 γδ T cells, particularly when engineered with chimeric antigen receptors (CARs), remains underexplored in solid tumors such as pancreatic cancer (PC), largely due to their low abundance in peripheral blood and challenges in ex vivo expansion. This study aims to directly compare the preclinical safety and efficacy among CAR-engineered Vδ1 γδ T cells, Vδ2 γδ T cells, and conventional αβ T cells.
View Article and Find Full Text PDFMethods Cell Biol
September 2025
Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Italy; CEINGE-Biotecnologie Avanzate, Naples, Italy.
Cystic fibrosis (CF) is a genetic disorder primarily known for its severe impact on lung function, but it also significantly affects the digestive system, leading to complications such as intestinal blockages, malabsorption, inflammation, and microbial dysbiosis. The study of CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) effects on intestinal physiology is critical for developing new effective treatments. This work highlights the use of the mouse intestine as a valuable model for analyzing cellular electrophysiology and CFTR function.
View Article and Find Full Text PDFJ Invest Dermatol
September 2025
Departamento de Biología Molecular, Instituto Universitario de Biología Molecular IUBM-UAM and Centro de Biología Molecular Severo Ochoa (UAM-CSIC), 28049 Madrid, Spain; Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain; CIBER de Enfermedades Cardiovasculares, ISCIII (CIBERCV
Tightly regulated cell-cell and cell-niche intercommunications via intertwined signaling networks are involved in maintaining normal hair follicle (HF) homeostasis, cycling and cell fate determination. However, knowledge of specific mechanisms by which hair loss takes place under pathological situations is needed. Using a keratinocyte-specific knockout mouse model, we uncover that the G-protein-coupled receptor kinase 2 (GRK2) signaling node plays a key role in HF homeostasis.
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