Immune checkpoint therapy targeting the PD-1/PD-L1 axis has revolutionized the treatment of solid tumors. However, T cell exhaustion underpins resistance to current anti-PD-1 therapies, resulting in lower response rates in cancer patients. CD28 is a T cell costimulatory receptor that can influence the PD-1 signalling pathway (and vice versa). CD28 signalling has the potential to counter T cell exhaustion by serving as a potential complementary response to traditional anti-PD-1 therapies. Here we discuss the interplay between PD-1 and CD28 in T cell immunotherapy and additionally how CD28 transcriptionally modulates T cell exhaustion. We also consider clinical attempts at targeting CD28; the challenges faced by past attempts and recent promising developments.
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http://dx.doi.org/10.1016/j.vph.2024.107461 | DOI Listing |
Cancer Immunol Res
January 2025
Sun Yat-sen University, Guangzhou, China.
Despite the pivotal role of cytotoxic T lymphocytes (CTLs) in anti-tumor immunity, a substantial proportion of CTL-rich hepatocellular carcinoma (HCC) patients experience early relapse or immunotherapy resistance. However, spatial immune variations impacting the heterogeneous clinical outcomes of CTL-rich HCCs remain poorly understood. Here, we compared the single-cell and spatial landscapes of 20 CTL-rich HCCs with distinct prognoses using multiplexed in situ staining and validated the prognostic value of myeloid spatial patterns in a cohort of 386 patients.
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January 2025
Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh EH16 4UU, UK.
To maintain and regenerate adult tissues after injury, division and differentiation of tissue-resident stem cells must be precisely regulated. It remains elusive which regulatory strategies prevent exhaustion or overgrowth of the stem cell pool, whether there is coordination between multiple mechanisms, and how to detect them from snapshots. In Drosophila testes, somatic stem cells transition to a state that licenses them to differentiate, but remain capable of returning to the niche and resuming cell division.
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January 2025
Department of Zoology, Graduate School of Science, Kyoto University, Sakyo, Kyoto, 606-8502, Japan.
Ascidian larval muscle cells present a classic example of autonomous development. A regulatory mechanism for these cells has been extensively investigated, and the regulatory gene circuit has been documented from maternal factors to a muscle-specific gene. In the present study, we comprehensively identified genes expressed specifically in ascidian muscle cells, and found that all of them are under control of a positive regulatory loop of Tbx6-r.
View Article and Find Full Text PDFActa Gastroenterol Belg
January 2025
Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium.
We report the case of a 59-year-old patient with a history of peripheral T-cell lymphoma, not otherwise specified (PTCLNOS) presenting with profuse diarrhea 3 months after completing lymphoma treatment. After exhaustive workup a recurrence of the peripheral T-cell lymphoma in the gastrointestinal tract was diagnosed. Predominant gastrointestinal recurrence is a unique presentation of relapse of PTCL-NOS.
View Article and Find Full Text PDFFront Cell Dev Biol
December 2024
Laboratory of Developmental Cardiology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czechia.
Fat mass and obesity-associated (FTO) protein, a key enzyme integral to the dynamic regulation of epitranscriptomic modifications in RNAs, significantly influences crucial RNA lifecycle processes, including splicing, export, decay, and translation. The role of FTO in altering the epitranscriptome manifests across a spectrum of physiological and pathological conditions. This review aims to consolidate current understanding regarding the implications of FTO in health and disease, with a special emphasis on its involvement in obesity and non-communicable diseases associated with obesity, such as diabetes, cardiovascular disease, and cancer.
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