yixinj

• Pati, Niladri Bhusan; Jin, Yixin; Kumar, Suman; Kyte, Jon A & Ciosk, Rafal (2025). Thermal potentiation improves IFN-γ production but not cytotoxicity in human CAR-T cells. BMC Research Notes. 18(1). doi: 10.1186/s13104-025-07249-5. Full text in Research Archive Show summary

  Objective Body temperature plays an important role in cancer, with febrile temperature generally associated with improved cancer resistance. In murine models, this resistance has been linked to the cytotoxic T cells, whose differentiation into cancer-killing effector cells is poor at lower but robust at elevated temperatures. If conserved, temperature-mediated potentiation of patient-derived T cells could be implemented to improve the existing cancer treatments, including the chimeric antigen receptor T-cell therapy (CAR T-cell therapy). Here, we tested this possibility using human STEAP1 CAR-T cells developed to target prostate cancer. Results In mice, transient exposure to febrile temperature (39–40 ºC) increases the production of IFN-γ and the cancer-killing ability of CD8 + T cells. Using a similar temperature treatment, we observed elevated levels of IFN-γ also in the human CAR-T cells. However, these cells displayed no improvement in their ability to kill cancer cells. Although we cannot discount the possibility that alternative protocols might lead to other outcomes, our findings suggest that incorporating thermal potentiation into existing protocols of CAR-T cell therapy may be more complicated than anticipated.

• Jin, Yixin; Dunn, Claire; Persiconi, Irene; Sike, Adam; Skorstad, Gjertrud & Beck, Carole Anne [Show all 7 contributors for this article] (2024). Comparative Evaluation of STEAP1 Targeting Chimeric Antigen Receptors with Different Costimulatory Domains and Spacers. International Journal of Molecular Sciences. ISSN 1661-6596. 25(1). doi: 10.3390/ijms25010586. Full text in Research Archive
• Beck, Carole Anne; Casey, Nicholas Paul; Persiconi, Irene; Moharrami, Neda Nejati; Sike, Adam & Jin, Yixin [Show all 7 contributors for this article] (2023). Development of a TGFβ—IL-2/15 Switch Receptor for Use in Adoptive Cell Therapy. Biomedicines. 11(2). doi: 10.3390/biomedicines11020459. Full text in Research Archive
• Jin, Yixin; Lorvik, Kristina Berg; Jin, Yang; Beck, Carole; Sike, Adam & Persiconi, Irene [Show all 10 contributors for this article] (2022). Development of STEAP1 targeting chimeric antigen receptor for adoptive cell therapy against cancer. Molecular Therapy Oncolytics. 26, p. 189–206. doi: 10.1016/j.omto.2022.06.007. Full text in Research Archive
• Pällmann, Nora; Ke, Deng; Livgård, Marte; Tesikova, Martina; Jin, Yixin & Frengen, Nicolai Sebastian [Show all 18 contributors for this article] (2021). Stress-mediated reprogramming of prostate cancer one-carbon cycle drives disease progression. Cancer Research. ISSN 0008-5472. 81(15), p. 4066–4078. doi: 10.1158/0008-5472.CAN-20-3956. Full text in Research Archive Show summary

  One-carbon (1C) metabolism has a key role in metabolic programming with both mitochondrial (m1C) and cytoplasmic (c1C) components. Here we show that activating transcription factor 4 (ATF4) exclusively activates gene expression involved in m1C, but not the c1C cycle in prostate cancer cells. This includes activation of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) expression, the central player in the m1C cycle. Consistent with the key role of m1C cycle in prostate cancer, MTHFD2 knockdown inhibited prostate cancer cell growth, prostatosphere formation, and growth of patient-derived xenograft organoids. In addition, therapeutic silencing of MTHFD2 by systemically administered nanoliposomal siRNA profoundly inhibited tumor growth in preclinical prostate cancer mouse models. Consistently, MTHFD2 expression is significantly increased in human prostate cancer, and a gene expression signature based on the m1C cycle has significant prognostic value. Furthermore, MTHFD2 expression is coordinately regulated by ATF4 and the oncoprotein c-MYC, which has been implicated in prostate cancer. These data suggest that the m1C cycle is essential for prostate cancer progression and may serve as a novel biomarker and therapeutic target. Significance: These findings demonstrate that the mitochondrial, but not cytoplasmic, one-carbon cycle has a key role in prostate cancer cell growth and survival and may serve as a biomarker and/or therapeutic target.

• Pällmann, Nora; Livgård, Marte; Tesikova, Martina; Nenseth, Hatice Zeynep; Akkus, Erman & Sikkeland, Jørgen [Show all 20 contributors for this article] (2019). Regulation of the unfolded protein response through ATF4 and FAM129A in prostate cancer. Oncogene. ISSN 0950-9232. 38, p. 6301–6318. doi: 10.1038/s41388-019-0879-2. Full text in Research Archive Show summary

  Cancer cells exploit many of the cellular adaptive responses to support their survival needs. One such critical pathway in eukaryotic cells is the unfolded protein response (UPR) that is important in normal physiology as well as disease states, including cancer. Since UPR can serve as a lever between survival and death, regulated control of its activity is critical for tumor formation and growth although the underlying mechanisms are poorly understood. Here we show that one of the main transcriptional effectors of UPR, activating transcription factor 4 (ATF4), is essential for prostate cancer (PCa) growth and survival. Using systemic unbiased gene expression and proteomic analyses, we identified a novel direct ATF4 target gene, family with sequence similarity 129 member A (FAM129A), which is critical in mediating ATF4 effects on prostate tumorigenesis. Interestingly, FAM129A regulated both PERK and eIF2α in a feedback loop that differentially channeled the UPR output. ATF4 and FAM129A protein expression is increased in patient PCa samples compared with benign prostate. Importantly, in vivo therapeutic silencing of ATF4-FAM129A axis profoundly inhibited tumor growth in a preclinical PCa model. These data support that one of the canonical UPR branches, through ATF4 and its target gene FAM129A, is required for PCa growth and thus may serve as a novel therapeutic target.

• Zakrzewska, Malgorzata; Haugsten, Ellen Margrethe; Nadratowska-Wesolowska, Beata; Oppelt, Angela; Hausott, Barbara & Jin, Yixin [Show all 9 contributors for this article] (2013). ERK-Mediated Phosphorylation of Fibroblast Growth Factor Receptor 1 on Ser(777) Inhibits Signaling. Science Signaling. ISSN 1945-0877. 6(262). doi: 10.1126/scisignal.2003087. Full text in Research Archive
• Zhen, Yan; Sørensen, Vigdis; Skjerpen, Camilla Skiple; Haugsten, Ellen Margrethe; Jin, Yixin & Waelchli, Sebastien [Show all 8 contributors for this article] (2012). Nuclear Import of Exogenous FGF1 Requires the ER-Protein LRRC59 and the Importins Kpn alpha 1 and Kpn beta 1. Traffic: The moving front of cell biology. ISSN 1398-9219. 13(5), p. 650–664. doi: 10.1111/j.1600-0854.2012.01341.x. Full text in Research Archive
• Jin, Yixin; Zhen, Yan; Haugsten, Ellen Margrethe & Wiedlocha, Antoni (2011). The driver of malignancy in KG-1a leukemic cells, FGFR1OP2-FGFR1, encodes an HSP90 addicted oncoprotein. Cellular Signalling. ISSN 0898-6568. 23(11), p. 1758–1766. doi: 10.1016/j.cellsig.2011.06.010. Full text in Research Archive
• Zakrzewska, Malgorzata; Sørensen, Vigdis; Jin, Yixin; Wiedlocha, Antoni & Olsnes, Sjur (2011). Translocation of exogenous FGF1 into cytosol and nucleus is a periodic event independent of receptor kinase activity. Experimental Cell Research. ISSN 0014-4827. 317(7), p. 1005–1015. doi: 10.1016/j.yexcr.2011.01.003. Full text in Research Archive
• Oz-Arslan, Devrim; Rüscher, Wolfgang; Myrtek, Daniel; Ziemer, Mirjana; Jin, Yixin & Damaj, Bassam B. [Show all 10 contributors for this article] (2006). IL-6 and IL-8 release is mediated via multiple signaling pathways after stimulating dendritic cells with lysophospholipids. Journal of Leukocyte Biology. ISSN 0741-5400. 80, p. 287–297. Full text in Research Archive
• Jin, Yixin; Damaj, Bassam & Maghazachi, Azzam (2005). Human resting CD16(-), CD16(+) and IL-2-, IL-12-, IL-15- or IFN-alpha-activated natural killer cells differentially respond to sphingosylphosphorylcholine, lysophosphatidylcholine and platelet-activating factor. European Journal of Immunology. ISSN 0014-2980. 35, p. 2699–2708. Full text in Research Archive Show summary

  The phosphorylcholine-containing lipid lysophosphatidylcholine (LPC) is abundant in the bloodstream, whereas sphingosylphosphorylcholine (SPC) and platelet-activating factor (PAF) highly accumulate at inflamed sites. Utilizing RT-PCR, flow cytometry and immunoblot analyses, we show for the first time that ovarian cancer G protein-coupled receptor 1, the receptor for SPC, is expressed in IL-2-, IL-12- and IL-15-activated but not in resting CD16-, resting CD16+ or IFN--activated NK cells. Similarly, G2 accumulation and PAF receptor are variably expressed in these subsets of NK cells. SPC, LPC and PAF differentially induce the chemotaxis of resting and activated NK cells. In the chemotaxis assay, it is observed that resting CD16-CD56bright and CD16+CD56dim cells predominantly respond to LPC, whereas activated NK cells, regardless of the sort of stimulus, robustly respond to PAF. SPC is also a potent chemoattractant for IL-2-, IL-12- and IL-15- but not for IFN--activated NK cells. Further analysis shows that, depending on the cytokine pattern of NK cell activation, phosphorylcholine-containing lipids differentially affect IFN- secretion by these cells. Our results provide one possible explanation for the tissue compartmentation of NK cells and their ability to secrete IFN-. Furthermore, these results may provide novel information regarding NK cell regulation during inflammation.

• Gauzzi, MC; Purificato, C; Donato, K; Jin, Yixin; Wang, Ling & Daniel, KC [Show all 10 contributors for this article] (2005). Suppressive effect of 1alpha,25-dihydroxyvitamin D3 on type I IFN-mediated monocyte differentiation into dendritic cells: impairment of functional activities and chemotaxis. Journal of Immunology. ISSN 0022-1767. 174(1), p. 270–276. Full text in Research Archive Show summary

  Dendritic cells (DCs) generated by a single-step exposure of human monocytes to type I IFN and GM-CSF (IFN-DCs) are endowed with potent immunostimulatory activities and a distinctive migratory response to specific chemokines. In this study, we evaluated the effects of 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the biologically active metabolite of vitamin D(3), on the DC differentiation/activation induced by type I IFN. We found that 1,25(OH)(2)D(3) prevented the generation of IFN-DCs when added to freshly isolated monocytes, and was capable of redirecting already differentiated IFN-DCs toward a more immature stage, as revealed by their immunophenotype, reduced allostimulatory activity, and impaired LPS-induced production of Th1-polarizing cytokines. Control and 1,25(OH)(2)D(3)-treated IFN-DCs exhibited a similar expression of vitamin D receptor, as well as comparable cell death rates. Furthermore, the chemotactic response of IFN-DCs to CCL4 and CCL19 was markedly reduced or completely abrogated by 1,25(OH)(2)D(3). Despite these changes in the IFN-DC migratory behavior, the expression of CCR5 and CCR7 and the calcium fluxes triggered by CCL4 and CCL19 were not affected. These findings indicate that, in this innovative single-step DC generation model from monocytes, the suppressive effect of 1,25(OH)(2)D(3) is associated with a potent impairment of DC migration in response to inflammatory and lymph node-homing chemokines, thus unraveling a novel mechanism involved in 1,25(OH)(2)D(3)-mediated immunomodulation.

• Maghazachi, Azzam; Knudsen, Eirunn; Jin, Yixin; Jenstad, Monica & Chaudhry, Farrukh Abbas (2004). D-galactosyl-b1-1' sphingosine and D-glucosyl-b1-1' sphingosine induce human natural killer cell apoptosis. Biochemical and Biophysical Research Communications - BBRC. ISSN 0006-291X. 320, p. 810–815. Full text in Research Archive
• Ling, Wang; Knudsen, Eirunn; Jin, Yixin; Gessani, S & Maghazachi, Azzam (2004). Lysophospholipids and chemokines activate distinct signal transduction pathways in T helper 1 and T helper 2 cells. Cellular Signalling. ISSN 0898-6568. 16(9), p. 991–1000. Full text in Research Archive
• Jin, Yixin; Knudsen, Eirunn; Wang, Ling; Bryceson, Yenan; Damaj, Bassam & Gessani, Sandra [Show all 7 contributors for this article] (2003). Sphingosine 1-phosphate is a novel inhibitor of T-cell proliferation. Blood. ISSN 0006-4971. 101(12), p. 4909–4915. Full text in Research Archive
• Jin, Yixin; Knudsen, Eirunn; Wang, Ling & Maghazachi, Azzam A. (2003). Lysophosphatidic acid induces human natural killer cell chemotaxis and intracellular calcium mobilization. European Journal of Immunology. ISSN 0014-2980. 33, p. 2083–2089. Full text in Research Archive Show summary

  We have investigated the effects of the bioactive lipid lysophosphatidic acid (LPA) on several functions of activated human natural killer (NK) cells. Flow cytometric and immunoblot analyses show that these cells express LPA(1, )LPA(2) and LPA(3). LPA but not its precursor phosphatidic acid (PA) induces the chemotaxis of NK cells, an activity that is inhibited by prior treatment of the cells with pertussis toxin (PTX). In addition, LPA induces the mobilization of intracellular calcium, an effect that is markedly inhibited by PTX, but is not inhibited by the addition of EGTA. PA also induces calcium flux in NK cells, but with much lower efficacy than LPA. Cross-desensitization experiments demonstrate that LPA and PA utilize different receptors. Moreover, LPA or PA but not sphingosine 1-phosphate, enhances IFN-gamma secretion by activated NK cells. Our results may shed some light on the findings that activated NK cells are found at the sites of tumor growth.

• Jin, Yixin; Knudsen, Eirunn; Wang, Ling; Bryceson, Yenan; Damaj, Bassam & Gessani, Sandra [Show all 7 contributors for this article] (2003). Sphingosine 1-phosphate is a novel inhibitor of T-cell proliferation. Blood. ISSN 0006-4971. 101, p. 4909–4915. Full text in Research Archive

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• Jin, Yixin; Dunn, Claire; Persiconi, Irene; Sike, Adam; Skorstad, Gjertrud & Beck, Carole Anne [Show all 7 contributors for this article] (2024). Correction to: Comparative Evaluation of STEAP1 Targeting Chimeric Antigen Receptors with Different Costimulatory Domains and Spacers (International Journal of Molecular Sciences, (2024), 25, 1, (586), 10.3390/ijms25010586). International Journal of Molecular Sciences. ISSN 1661-6596. 25(18). doi: 10.3390/ijms251810024. Full text in Research Archive

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