Clinical and translational discovery最新文献

{"title":"The role of T cells in sepsis of distinct infectious aetiologies","authors":"Xuanqi Liu,&nbsp;Bijun Zhu,&nbsp;Wanxin Duan,&nbsp;Ruixiang Kang,&nbsp;Xiangdong Wang,&nbsp;Liyang Li","doi":"10.1002/ctd2.70125","DOIUrl":"https://doi.org/10.1002/ctd2.70125","url":null,"abstract":"<p>Sepsis is a complex and life-threatening syndrome resulting from infection and characterized by dysregulated host immune responses. T cells play a central role in orchestrating immune defence against pathogens, yet their function undergoes profound alterations during sepsis. The impact of sepsis on T cell function varies depending on the causative pathogen. T cells exhibit an initial hyperactivation phase in bacterial sepsis, followed by a state of exhaustion, characterised by reduced cytokine production, impaired proliferation, and metabolic dysfunction. Such disorders are associated with disruptions in T cell receptor signalling, upregulation of immune checkpoint molecules such as PD-1 and CTLA4, and mitochondrial damage. T cell dysfunction is often linked to immunosuppression in viral sepsis, with an inhibition of antiviral responses and induction of immune tolerance. The distinct immune evasion strategies impair T cell-mediated pathogen clearance in viral sepsis, while altered T cell subsets are observed in fungal and parasitic sepsis. Such immune dysregulations exacerbate sepsis-induced immune suppression, increase susceptibility to secondary infections, and worsen clinical outcomes. Elucidating the pathogen-specific pathways that underlie T cell dysfunction in sepsis is crucial for the development of precise immunotherapies. These insights could inform the design of therapeutic strategies aimed at restoring T cell function and improving the prognosis of septic patients.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147569522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumour hepcidin levels as a biomarker for predicting response to immune checkpoint inhibition in advanced non-small cell lung cancer","authors":"Yuichiro Suzukawa,&nbsp;Masaki Yamamoto,&nbsp;Shuhei Teranishi,&nbsp;Sosuke Kubo,&nbsp;Makoto Kudo,&nbsp;Takeshi Kaneko","doi":"10.1002/ctd2.70129","DOIUrl":"https://doi.org/10.1002/ctd2.70129","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepcidin, a key regulator of iron homeostasis, is often overexpressed in non-small cell lung cancer (NSCLC). While hepcidin renders cells susceptible to ferroptosis, which is linked to the activity of programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors, its clinical impact on immunotherapy efficacy remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed patients with advanced NSCLC who received anti-PD-1/PD-L1 monotherapy. Patients were stratified into two groups based on immunohistochemical analysis: high hepcidin expression (tumour proportion score [TPS] = 50%, n = 6) and none-to-moderate expression (TPS 0–49%, n = 39). Treatment duration, progression-free survival (PFS), and overall survival (OS) were compared. In vitro mechanisms were also explored using hepcidin and interferon-gamma (IFNg) co-culture models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The high-hepcidin group exhibited a longer median treatment duration (42 vs. 5 days;\t<i>p</i> = 0.051). This group also showed improved PFS (2222 vs. 126 days; hazard ratio [HR], 0.35 [95% CI, 0.16–0.79]; <i>p</i> = 0.0643) and OS (not reached vs. 459 days; HR, 0.46 [95% CI, 0.18–1.16]; <i>p</i> = 0.0994), although these differences did not reach statistical significance. In vitro experiments revealed that hepcidin enhanced IFNg-induced reactive oxygen species production and cytotoxicity in A549 cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Advanced NSCLC patients with high hepcidin expression may derive greater benefit from anti-PD-1/PD-L1 monotherapy. Our findings suggest that cellular sensitivity to IFNg varies by hepcidin expression levels.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147299984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overcoming challenges in CAR-T therapy for malignancies: Mechanisms and strategies","authors":"Yushan Huang,&nbsp;Jun Long,&nbsp;Changpeng Yang,&nbsp;Wang Lu,&nbsp;Husheng Mei,&nbsp;Wenbin Qian,&nbsp;Jing Yang,&nbsp;Aibin Liang","doi":"10.1002/ctd2.70045","DOIUrl":"https://doi.org/10.1002/ctd2.70045","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chimeric Antigen Receptor T-cell (CAR-T) therapy has evolved from its initial application in hematological cancers to treating solid tumors and autoimmune diseases. Despite iterative advancements in CAR design improving efficacy and safety, challenges including limited persistence, immune-related toxicities, tumor resistance mechanisms, and barriers posed by the tumor microenvironment (TME) remain critical obstacles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review synthesizes current evidence on CAR-T resistance mechanisms and therapeutic strategies. Key approaches analyzed include CAR design optimization (e.g., dual-targeting), pre-infusion tumor burden reduction, combination therapies to mitigate immune suppression, and cytokine support (e.g., IL-2/IL-15) to enhance persistence. The role of the TME (hypoxia, metabolic competition, immunosuppressive factors) and tumor-intrinsic resistance drivers (antigen loss, anti-apoptotic signaling) are systematically evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Major resistance mechanisms include antigen escape (masking/loss), high tumor burden, and TME-mediated suppression (hypoxia, immune checkpoints). Clinical challenges involve manufacturing delays, insufficient CAR-T cytotoxicity, and poor persistence. Strategies such as dual-target CARs, preconditioning regimens, and cytokine-augmented persistence demonstrate preclinical/clinical promise in overcoming these limitations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CAR-T therapy holds transformative potential but requires addressing resistance and toxicity barriers. Future directions include allogeneic CAR-T platforms, in vivo CAR-T delivery, and novel combinatorial approaches. While these innovations offer exciting prospects, scalability, safety, and long-term efficacy necessitate further translational and clinical research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surufatinib plus anti-PD-1/PD-L1 antibody as second-line therapy for advanced biliary tract cancer: A single-centre investigator-initiated trial","authors":"Xinni Chen,&nbsp;Feng Wang,&nbsp;Yuan Cheng,&nbsp;Mengran Cao,&nbsp;Kuimin Mei,&nbsp;Xiaoyuan Chu,&nbsp;Fang Dai,&nbsp;Xinlei Gong","doi":"10.1002/ctd2.70123","DOIUrl":"https://doi.org/10.1002/ctd2.70123","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To explore the efficacy and safety of surufatinib in combination with anti-PD-1/PD-L1 antibodies (with or without chemotherapy) in patients with advanced BTC after failure of first-line treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>24 patients with advanced BTC who failed first-line treatment were admitted to our centre from March 2023 to August 2024 and treated with surufatinib combined with anti-PD-1/PD-L1 antibodies (with or without chemotherapy). The primary endpoint was PFS, and the secondary endpoints were ORR, DCR, OS and safety indicators.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were 10 cases of intrahepatic cholangiocarcinoma, 5 cases of hilar cholangiocarcinoma, 2 cases of extrahepatic cholangiocarcinoma, and 7 cases of gallbladder cancer. There were 16 cases of combined chemotherapy and immunotherapy, and 8 cases of combined immunotherapy alone. The median PFS of all patients was 3.81 months (95%CI 2.46–4.50), the median OS was 10.48 months (95%CI 6.54–16.43), and the ORR was 20.8% (95%CI 7.1%–42.2%). The DCR was 54.2% (95%CI 32.8%–74.4%). Subgroup analysis showed that the median PFS of cholangiocarcinoma group was 3.81months (95%CI 2.07–4.50), while the median OS was 9.56months (95%CI 6.34–16.43). The median PFS of gallbladder cancer was 3.81 months (95%CI 2.07–4.50), while the OS was 11.11 months (95%CI 3.42–11.11). The median PFS in the combined chemotherapy plus immunization group was 3.91months (95%CI 2.46–5.16), and the median OS was 8.80 months (95%CI 6.34–16.34). The median PFS in the combined immunotherapy alone group was 3.22 months (95%CI 1.08–4.70), and the median OS was 10.48 months (95%CI 2.53–11.2). TRAE occurred in 15 cases (62.5%) which mainly including hypothyroidism, transaminase elevation and fatigue. While the incidence of grade 3 and above AE was 12.5% (3/24), mainly including leukopenia and thrombocytopenia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Surufatinib combined with anti PD-1/PD-L1 antibodies was effective and tolerable in second-line treatment of advanced BTC. It is worthy of further in-depth exploration through multi-centre and large-sample clinical trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146216933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CEACAM6 silencing suppresses tumour growth and sensitises cholangiocarcinoma to cisplatin","authors":"Shi-Jia Dai,&nbsp;Jiang-Qi Tan,&nbsp;Jia-Qi Guo,&nbsp;Ya-Nan Zhou,&nbsp;Teng Huang,&nbsp;Hao-Lin Jiang,&nbsp;Yang Liu,&nbsp;Li-Wei Dong,&nbsp;Zhen-Gang Yuan","doi":"10.1002/ctd2.70126","DOIUrl":"https://doi.org/10.1002/ctd2.70126","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The CEACAM family, a major subgroup of the carcinoembryonic antigen (CEA) family, is widely expressed in normal and neoplastic tissues. Although CEACAM6 overexpression has been reported in cholangiocarcinoma (CCA), the molecular mechanisms by which it modulates chemosensitivity in CCA remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We began by analysing CEACAM6 expression in CCA using the TCGA database, then confirmed its clinical relevance in our institutional patient cohorts. Through cellular assays, animal models, and RNA sequencing, we found that silencing CEACAM6 inhibits tumour growth and identified its key underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our data showed that CEACAM6 expression is significantly elevated in CCA and serves as an independent prognostic marker. Functional validation by CEACAM6 silencing demonstrated that loss of CEACAM6 markedly suppressed tumour cell proliferation and clonogenicity in vitro, potentiated cisplatin-induced DNA damage and apoptosis, and inhibited tumour growth in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CEACAM6 silencing was shown to suppress ribosome biogenesis and augment DNA damage, thereby inhibiting tumour growth and sensitising CCA to cisplatin. Our research highlights CEACAM6 as a potential therapeutic target that could help improve the therapeutic efficacy of cisplatin in CCA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146216834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral blood smear analysis: A comparison of GPT-4o and supervised deep learning models","authors":"Mobina Shrestha,&nbsp;Salina Dahal,&nbsp;Vishal Mandal,&nbsp;Amir Babu Shrestha","doi":"10.1002/ctd2.70124","DOIUrl":"https://doi.org/10.1002/ctd2.70124","url":null,"abstract":"&lt;p&gt;Peripheral blood smear review remains pivotal to hematologic diagnosis. Morphologic abnormalities central to contemporary hematologic classification, including blasts, dysplastic neutrophils, nucleated red blood cells, and abnormal platelets, remain critical to diagnosis under both the World Health Organisation&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; and the International Consensus Classification frameworks.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; While automated analysers have improved workflow and standardisation in cell counting, they often fall short in detecting key morphological features. These diagnostic gaps make smear interpretation by trained personnel indispensable in both routine and urgent haematology. However, access to expert haematological review is variable, and manual interpretation is time-intensive and subject to interobserver variability. This has led to increasing interest in artificial intelligence (AI) systems that can support or automate morphologic assessment by learning from large sets of labelled smear images.&lt;/p&gt;&lt;p&gt;Recent advances in machine learning have enabled the development of models capable of classifying peripheral blood cells from digital images with high accuracy. Convolutional neural networks and transformer-based architectures have shown promise in this domain, achieving expert-level performance when trained on large, curated datasets.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; However, these supervised models rely on thousands of annotated examples for each cell type and often require fine-tuning before deployment. In most clinical settings, such resources are not readily available, and differences in staining, imaging, and labelling practices further limit generalizability across institutions. As a result, the practical application of supervised AI models remains dependent on the availability of large amounts of annotated data in addition to high-performance computing.&lt;/p&gt;&lt;p&gt;Therefore, to address these limitations, recent studies have explored models that require far less annotated data to perform diagnostic tasks. One such approach is few-shot learning, where the model is shown a small number of labelled examples at the time of evaluation rather than being retrained. This mirrors how clinicians often reason, by comparing current findings to a mental archive of similar cases rather than relearning each diagnosis from first principles. Early applications of this method in pathology and radiology have shown that such models can perform well even with limited supervision, including recent works demonstrating label-efficient classification in general oncology.&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; However, this strategy has not been evaluated in haematology, where morphologic subtleties often distinguish closely related cell types.&lt;/p&gt;&lt;p&gt;Recent reviews have highlighted the ongoing transition of hematopathology from conventional light microscopy toward digital and computationally enabled workflows, in which peripheral blood films are increasingly analysed as struc","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146216223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota and central nervous system's direct bidirectional regulation: The mechanisms of the gut–brain axis in irritable bowel syndrome","authors":"Jinxia Zhai,&nbsp;Yingjie Li,&nbsp;Jiameng Liu,&nbsp;Cong Dai","doi":"10.1002/ctd2.70117","DOIUrl":"https://doi.org/10.1002/ctd2.70117","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Irritable bowel syndrome (IBS) is a prevalent condition in which disrupted communication between the gut and the brain plays a central role in disease manifestation. A dynamic, bidirectional regulatory network links the gut microbiota with the central nervous system (CNS), commonly referred to as the gut–brain axis, and this network exerts broad influence over both gastrointestinal physiology and psychological states.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This review specifically concentrates on direct microbiota–CNS communication pathways in the context of IBS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This narrative review synthesizes existing experimental and clinical evidence related to gut microbiota–brain interactions, with a particular focus on neural and neuroendocrine signaling mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Gut microorganisms affect CNS function via microbial metabolites and neural signalling routes, whereas the CNS modulates gastrointestinal activity through integrated neural and endocrine pathways, involving the autonomic nervous system and the enteric nervous system. Given the complexity of these reciprocal interactions, this review specifically concentrates on direct microbiota–CNS communication pathways, with particular attention to neural circuits and the hypothalamic–pituitary–adrenal axis in the context of IBS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Furthermore, we discuss how advances in precision stratification and multi-omics approaches may facilitate the development of personalized therapeutic strategies, ultimately improving symptom control and restoring balance between gut microbial ecosystems and neural regulation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146216850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPR183-mediated activation of PI3K is a potential biomarker for immunotherapy in lung cancer","authors":"Ling Ye,&nbsp;Nannan Zheng,&nbsp;Fangming Liu,&nbsp;Huirong Fu,&nbsp;Yifei Liu,&nbsp;Ying Yang,&nbsp;Ruixue Qi,&nbsp;Duojiao Wu,&nbsp;Lin Shi,&nbsp;Dongli Song","doi":"10.1002/ctd2.70119","DOIUrl":"https://doi.org/10.1002/ctd2.70119","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>As one of commonly used immune checkpoint inhibition therapies, PD1 monoclonal antibodies exhibit a promising cancer immunotherapy approach. However, their efficacy on tumour immunity needs to be augment, as large numbers of patients poorly respond to the treatment or suffer from recurrence in clinical. Although pan-PI3K is involved in the performance of PD1 on T cell immunity, the study for mechanisms of PI3K subunits involved in could be helpful for proposing a potential treatment strategy for lung cancer that combines anti-PD1 treatment with PI3Kγ inhibitor.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials &amp; answers</h3>\u0000 \u0000 <p>Alterations of CD4⁺ and CD8⁺ T cell subpopulations in 11 types of peripheral blood mononuclear cells with healthy subjects and cancer patients were examined. The efficacy of different treatment strategies for lung cancer was then investigated, and the factors affecting the efficacy of anti-PD1 therapy in lung cancer were discussed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Lung cancer is characterized by widespread variation in T cell subsets, and anti-PD1 treatment is effective against CD4⁺ Tcm, CD4⁺ Tem and CD4⁺ Tn cell subsets. The involvement of PI3K in the effect of anti-PD1 was demonstrated using single-cell RNA sequencing. The PI3Kγ inhibitor CAY10505 was effective against CD4⁺ Tcm and CD4⁺ Tn subsets in lung cancer in vitro but not in pan-cancer therapy, indicating that the therapeutic effect of PI3Kγ on CD4⁺ T cells was lung cancer-specific. G-protein coupled receptor 183 (<i>GPR183</i>) was involved in migration and positioning of immune cells and associated with various immune-related diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>We explored the regulatory role of <i>GPR183</i> in the PI3K pathway and T cell subsets and identified potential lipids involved using lipidomics. We found that inhibition of PI3Kγ upregulated CD4⁺ Tcm and CD4⁺ Tn, potentially enhancing the therapeutic efficacy of anti-PD1 antibodies. Combining anti-PD1 treatment with PI3Kγ inhibitor could be a potential treatment strategy for lung cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The emerging role of CAMK1D in diabetes, metabolism and feeding behaviours: A mechanistic systematic review","authors":"Livio Tarchi,&nbsp;Annalisa Di Giacomo,&nbsp;Lorenzo Bonacchi,&nbsp;Andrea Di Santo,&nbsp;Paolo Rovero,&nbsp;Chiara Sassoli,&nbsp;Rachele Garella,&nbsp;Roberta Squecco,&nbsp;Gianluca Villa,&nbsp;Romina Nassini,&nbsp;Francesco De Logu,&nbsp;Tiziana Pisano,&nbsp;Valdo Ricca,&nbsp;Giovanni Castellini","doi":"10.1002/ctd2.70120","DOIUrl":"https://doi.org/10.1002/ctd2.70120","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diabetes, metabolic disorders and feeding behaviours continue to pose significant public health challenges. Calcium/calmodulin-dependent protein kinase ID (CAMK1D) has recently emerged as a pivotal molecule potentially bridging peripheral metabolic control with central appetite regulation. Therefore, a comprehensive review was performed to critically evaluate and synthesize current evidence regarding the role of CAMK1D in diabetes, metabolic processes and feeding behaviours.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Main text</h3>\u0000 \u0000 <p>The review assessed both published results (263 non-duplicate studies; across Pubmed, WebOfScience and EMBASE) and the grey literature (including 14 patents, 3 clinical trials). Results from 43 unique studies, 2 patents and 5 genome-wide association studies were finally summarized. CAMK1D modulates both metabolic processes and feeding behaviours, exhibiting tissue-specific dynamics and diverging regulatory control either in the central nervous system (i.e., hypothalamic nuclei regulating appetite and satiety) or in the periphery (i.e., pancreatic beta cells). Genetic studies highlighted significant associations between CAMK1D polymorphisms and increased susceptibility to diabetes, obesity and altered feeding behaviours.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CAMK1D represents an emerging molecular target with promising implications for the treatment of a wide range of clinical conditions. However, further large-scale, mechanistic and longitudinal studies are warranted to validate its role across physiological and pathophysiological conditions, as well as to explore its future therapeutic potential.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell sequencing for cancer precision medicine: From mechanism discovery to diagnosis and therapeutics","authors":"Yue Zhao,&nbsp;Hancong Li,&nbsp;Huanzuo Yang,&nbsp;Gongshuang Zhang,&nbsp;Xinyue Fu,&nbsp;Peiheng Li,&nbsp;Puxing He,&nbsp;Shuang Wu,&nbsp;Han Luo","doi":"10.1002/ctd2.70114","DOIUrl":"https://doi.org/10.1002/ctd2.70114","url":null,"abstract":"<p>Tumour heterogeneity, encompassing genetic, epigenetic, and microenvironmental diversity, remains a fundamental obstacle in precision oncology. Traditional bulk sequencing captures only averaged molecular profiles, thereby masking rare yet functionally critical subpopulations that drive malignant progression and therapeutic resistance. Recently, the emergence of single-cell sequencing technologies has overcome the limitations of bulk approaches, enabling high-resolution analyses of the genome, transcriptome, epigenome and proteome at the single-cell level. These advances have enabled detailed mapping of tumour ecosystems, identification of key cellular subtypes, reconstruction of evolutionary trajectories and elucidation of intercellular communication networks within the tumour microenvironment. Accumulating evidence demonstrates that single-cell technologies elucidate fundamental aspects of tumour biology and reveal potential diagnostic and therapeutic targets. This review systematically summarises the recent advances and applications of single-cell sequencing in the field of precision oncology, with particular emphasis on its applications in mechanistic discovery, diagnosis, therapy, and prognosis. Furthermore, we discuss current challenges related to technology, data analysis, and clinical translation, and outline future research directions. In summary, single-cell sequencing has profoundly reshaped our understanding of tumour biology and is propelling oncology into a new era of precision, prediction, and personalisation.</p>","PeriodicalId":72605,"journal":{"name":"Clinical and translational discovery","volume":"6 1","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctd2.70114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}