Adoptive cell therapy (ACT) using tumor-reactive T cells is a promising form of immunotherapy to specifically target cancer. However, the survival and functional maintenance of adoptively transferred T cells remains a challenge, ultimately limiting their efficacy. Here, we evaluated the use of recombinant IL7-Fc in ACT. In a lymphopenic murine melanoma model, IL7-Fc treatment led to the enhanced inhibition of tumor growth with an increased number of adoptively transferred CD8 T cells in tumor tissue and tumor-draining lymph nodes. Additionally, IL7-Fc further enhanced anti-tumor responses that were induced by recombinant human IL2 in the same mouse model. In contrast, in an immunocompetent murine melanoma model, IL7-Fc dampened the anti-tumor immunity. Further, IL7-Fc decreased the proliferation of adoptively transferred and immune-activated tumor-reactive CD8 T cells in immunocompetent mice by inducing the massive expansion of endogenous T cells, thereby limiting the space for adoptively transferred T cells. Our data suggest that IL7-Fc is principally beneficial for enhancing the efficacy of tumor-reactive T-cells in lymphopenic conditions for the ACT.
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http://dx.doi.org/10.3390/cells10082018 | DOI Listing |
Nature
January 2025
Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
This study examines the origin and differentiation of stem-like CD8+ T cells that are essential for sustained T cell immunity in chronic viral infections and cancer and also play a key role in PD-1 directed immunotherapy. These PD-1+ TCF-1+ TOX+ stem-like CD8+ T cells, also referred to as precursors of exhausted T cells, have a distinct program that allows them to adapt to chronic antigen stimulation. Using the mouse model of chronic LCMV infection we found that virus specific stem-like CD8+ T cells are generated early (day 5) during chronic infection suggesting that this crucial fate commitment occurs irrespective of infection outcome.
View Article and Find Full Text PDFNeurogastroenterol Motil
January 2025
Center for Intestinal Neuro-Immune Interactions, Translational Research Center for GI Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
Introduction: Postoperative ileus (POI) is an iatrogenic disorder marked by temporary impaired gastrointestinal (GI) motility post-abdominal surgery. Surgical handling of the intestine activates resident macrophages (Mfs), leading to inflammatory cytokine release and leukocyte recruitment into the muscularis, which compromises intestinal contractility. The mechanisms behind this activation are unclear.
View Article and Find Full Text PDFFront Immunol
January 2025
Molecular Immunology and Gene Therapy, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Generation of high avidity T cell receptors (TCRs) reactive to tumor-associated antigens (TAA) is impaired by tolerance mechanisms, which is an obstacle to effective T cell therapies for cancer treatment. NY-ESO-1, a human cancer-testis antigen, represents an attractive target for such therapies due to its broad expression in different cancer types and the restricted expression in normal tissues. Utilizing transgenic mice with a diverse human TCR repertoire, we isolated effective TCRs against NY-ESO-1 restricted to HLA-A*02:01.
View Article and Find Full Text PDFJCI Insight
January 2025
Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, United States of America.
The nucleus accumbens-associated protein-1 (NAC1) has recently emerged as a pivotal factor in oncogenesis by promoting glycolysis. Deletion of NAC1 in regulatory T cells (Tregs) has been shown to enhance FoxP3 stability, a suppressor of glycolysis. This study delves into the intriguing dual role of NAC1, uncovering that Tregs-specific deletion of NAC1 fosters metabolic fitness in Tregs, thereby promoting tumorigenesis.
View Article and Find Full Text PDFPharmaceutics
December 2024
Laboratory for Fetal and Regenerative Biology, Department of Surgery, University of Arizona Tucson College of Medicine, Banner Children's at Diamond Children's Medical Center, 1656 E Mabel St, Rm 230, Tucson, AZ 85721, USA.
Dysregulated inflammation and oxidative stress are strongly implicated in the pathogenesis of inflammatory bowel disease. We have developed a novel therapeutic that targets inflammation and oxidative stress. It is comprised of microRNA-146a (miR146a)-loaded cerium oxide nanoparticles (CNPs) (CNP-miR146a).
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