来自用户 大勇 的文献。
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1.
大勇 (2023-11-30 21:45):
#paper https://doi.org/10.1038/s41586-023-05710-8 Nassour, J., Aguiar, L.G., Correia, A. et al. Telomere-to-mitochondria signalling by ZBP1 mediates replicative crisis. Nature 614, 767–773 (2023). 这篇文献主要是发现了永生化细胞不死的机制,通过讲端粒、衰老和和免疫结合起来,从侧面为肿瘤细胞的异常增殖提供了新的思路。全文仅仅用了简单的WB和免疫荧光等技术,完成了比较有创新性的课题并发表在了nature上。整篇文献发现永生化细胞中ZBP1表达升高和I型干扰素信号通路激活,通过分析发现ZBP1可以与端粒不稳定相关RNA结合并定位于线粒体上,从而激活MAVS和下游I型干扰素信号通路维持细胞的生长,而端粒的不稳定又会激活cGAS信号通路,引起I型干扰素信号通路激活导致ZBP1升高,从而形成了一个环路。
IF:50.500Q1 Nature, 2023-02. DOI: 10.1038/s41586-023-05710-8 PMID: 36755096
Abstract:
Cancers arise through the accumulation of genetic and epigenetic alterations that enable cells to evade telomere-based proliferative barriers and achieve immortality. One such barrier is replicative crisis-an autophagy-dependent program that … >>>
Cancers arise through the accumulation of genetic and epigenetic alterations that enable cells to evade telomere-based proliferative barriers and achieve immortality. One such barrier is replicative crisis-an autophagy-dependent program that eliminates checkpoint-deficient cells with unstable telomeres and other cancer-relevant chromosomal aberrations. However, little is known about the molecular events that regulate the onset of this important tumour-suppressive barrier. Here we identified the innate immune sensor Z-DNA binding protein 1 (ZBP1) as a regulator of the crisis program. A crisis-associated isoform of ZBP1 is induced by the cGAS-STING DNA-sensing pathway, but reaches full activation only when associated with telomeric-repeat-containing RNA (TERRA) transcripts that are synthesized from dysfunctional telomeres. TERRA-bound ZBP1 oligomerizes into filaments on the outer mitochondrial membrane of a subset of mitochondria, where it activates the innate immune adapter protein mitochondrial antiviral-signalling protein (MAVS). We propose that these oligomerization properties of ZBP1 serve as a signal amplification mechanism, where few TERRA-ZBP1 interactions are sufficient to launch a detrimental MAVS-dependent interferon response. Our study reveals a mechanism for telomere-mediated tumour suppression, whereby dysfunctional telomeres activate innate immune responses through mitochondrial TERRA-ZBP1 complexes to eliminate cells destined for neoplastic transformation. <<<
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2.
大勇 (2023-10-31 22:35):
#paper https://doi.org/10.1038/s41586-020-2682-1 Cancer SLC43A2 alters T cell methionine metabolism and histone methylation 本文献以甲硫氨酸代谢为主要内容,肿瘤细胞通过SLC48A2转运体与CD8+T细胞竞争甲硫氨酸,导致T细胞甲硫氨酸摄取减少,从而影响甲硫氨酸代谢,抑制组蛋白H3K79me2,进而抑制了STAT5的通路激活,最终导致CD8+T细胞杀伤功能减退和凋亡增多。
IF:50.500Q1 Nature, 2020-09. DOI: 10.1038/s41586-020-2682-1 PMID: 32879489
Abstract:
Abnormal epigenetic patterns correlate with effector T cell malfunction in tumours, but the cause of this link is unknown. Here we show that tumour cells disrupt methionine metabolism in CD8 … >>>
Abnormal epigenetic patterns correlate with effector T cell malfunction in tumours, but the cause of this link is unknown. Here we show that tumour cells disrupt methionine metabolism in CD8 T cells, thereby lowering intracellular levels of methionine and the methyl donor S-adenosylmethionine (SAM) and resulting in loss of dimethylation at lysine 79 of histone H3 (H3K79me2). Loss of H3K79me2 led to low expression of STAT5 and impaired T cell immunity. Mechanistically, tumour cells avidly consumed methionine and outcompeted T cells for methionine by expressing high levels of the methionine transporter SLC43A2. Genetic and biochemical inhibition of tumour SLC43A2 restored H3K79me2 in T cells, thereby boosting spontaneous and checkpoint-induced tumour immunity. Moreover, methionine supplementation improved the expression of H3K79me2 and STAT5 in T cells, and this was accompanied by increased T cell immunity in tumour-bearing mice and patients with colon cancer. Clinically, tumour SLC43A2 correlated negatively with T cell histone methylation and functional gene signatures. Our results identify a mechanistic connection between methionine metabolism, histone patterns, and T cell immunity in the tumour microenvironment. Thus, cancer methionine consumption is an immune evasion mechanism, and targeting cancer methionine signalling may provide an immunotherapeutic approach. <<<
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3.
大勇 (2023-09-30 19:42):
#paper A membrane-associated MHC-I inhibitory axis for cancer immune evasion Cell August 08, 2023DOI:https://doi.org/10.1016/j.cell.2023.07.016 这篇文献使用CRISPR的文库筛选方法,通过构建特异性抗原提呈模型筛选与MHCI特异性调控相关的因子,并通过机制分析和表型探索,发现了STW复合物对其的自噬降解调控作用
IF:45.500Q1 Cell, 2023-08-31. DOI: 10.1016/j.cell.2023.07.016 PMID: 37557169
Abstract:
Immune-checkpoint blockade has revolutionized cancer treatment, but some cancers, such as acute myeloid leukemia (AML), do not respond or develop resistance. A potential mode of resistance is immune evasion of … >>>
Immune-checkpoint blockade has revolutionized cancer treatment, but some cancers, such as acute myeloid leukemia (AML), do not respond or develop resistance. A potential mode of resistance is immune evasion of T cell immunity involving aberrant major histocompatibility complex class I (MHC-I) antigen presentation (AP). To map such mechanisms of resistance, we identified key MHC-I regulators using specific peptide-MHC-I-guided CRISPR-Cas9 screens in AML. The top-ranked negative regulators were surface protein sushi domain containing 6 (SUSD6), transmembrane protein 127 (TMEM127), and the E3 ubiquitin ligase WWP2. SUSD6 is abundantly expressed in AML and multiple solid cancers, and its ablation enhanced MHC-I AP and reduced tumor growth in a CD8 T cell-dependent manner. Mechanistically, SUSD6 forms a trimolecular complex with TMEM127 and MHC-I, which recruits WWP2 for MHC-I ubiquitination and lysosomal degradation. Together with the SUSD6/TMEM127/WWP2 gene signature, which negatively correlates with cancer survival, our findings define a membrane-associated MHC-I inhibitory axis as a potential therapeutic target for both leukemia and solid cancers. <<<
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大勇 (2023-08-31 23:51):
#paper Correia, A.L., Guimaraes, J.C., Auf der Maur, P. et al. Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy. Nature 594, 566-571 (2021). https://doi.org/10.1038/s41586-021-03614-z 该文章主要讲述的是乳腺癌肝转移时存在着休眠期细胞,党癌细胞的休眠期解除时,则会引起癌细胞的复发和转移,乳腺癌在肝脏的休眠过程可能由NK细胞分泌IFNγ来维持,而当肝脏星形细胞分泌CXCL12抑制NK细胞时,则会解除这个状态,使休眠细胞继续激活扩增。
IF:50.500Q1 Nature, 2021-06. DOI: 10.1038/s41586-021-03614-z PMID: 34079127
Abstract:
The persistence of undetectable disseminated tumour cells (DTCs) after primary tumour resection poses a major challenge to effective cancer treatment. These enduring dormant DTCs are seeds of future metastases, and … >>>
The persistence of undetectable disseminated tumour cells (DTCs) after primary tumour resection poses a major challenge to effective cancer treatment. These enduring dormant DTCs are seeds of future metastases, and the mechanisms that switch them from dormancy to outgrowth require definition. Because cancer dormancy provides a unique therapeutic window for preventing metastatic disease, a comprehensive understanding of the distribution, composition and dynamics of reservoirs of dormant DTCs is imperative. Here we show that different tissue-specific microenvironments restrain or allow the progression of breast cancer in the liver-a frequent site of metastasis that is often associated with a poor prognosis. Using mouse models, we show that there is a selective increase in natural killer (NK) cells in the dormant milieu. Adjuvant interleukin-15-based immunotherapy ensures an abundant pool of NK cells that sustains dormancy through interferon-γ signalling, thereby preventing hepatic metastases and prolonging survival. Exit from dormancy follows a marked contraction of the NK cell compartment and the concurrent accumulation of activated hepatic stellate cells (aHSCs). Our proteomics studies on liver co-cultures implicate the aHSC-secreted chemokine CXCL12 in the induction of NK cell quiescence through its cognate receptor CXCR4. CXCL12 expression and aHSC abundance are closely correlated in patients with liver metastases. Our data identify the interplay between NK cells and aHSCs as a master switch of cancer dormancy, and suggest that therapies aimed at normalizing the NK cell pool might succeed in preventing metastatic outgrowth. <<<
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大勇 (2023-07-31 23:24):
#paper Bergholz, J.S., Wang, Q., Wang, Q. et al. PI3Kβ controls immune evasion in PTEN-deficient breast tumours. Nature 617, 139-146 (2023). https://doi.org/10.1038/s41586-023-05940-w 这篇文献在机制方面并没有深入研究,但却是有很好的临床转化前景,在PTEN缺失的肿瘤中,PI3K发挥着重要作用,作者发现其中PI3Kβ是引起该类肿瘤免疫抑制的关键分子,靶向PI3Kβ-BMX-STAT3信号通路可以有效逆转免疫抑制的状态,而且可以促进免疫治疗的疗效
IF:50.500Q1 Nature, 2023-05. DOI: 10.1038/s41586-023-05940-w PMID: 37076617
Abstract:
Loss of the PTEN tumour suppressor is one of the most common oncogenic drivers across all cancer types. PTEN is the major negative regulator of PI3K signalling. The PI3Kβ isoform … >>>
Loss of the PTEN tumour suppressor is one of the most common oncogenic drivers across all cancer types. PTEN is the major negative regulator of PI3K signalling. The PI3Kβ isoform has been shown to play an important role in PTEN-deficient tumours, but the mechanisms underlying the importance of PI3Kβ activity remain elusive. Here, using a syngeneic genetically engineered mouse model of invasive breast cancer driven by ablation of both Pten and Trp53 (which encodes p53), we show that genetic inactivation of PI3Kβ led to a robust anti-tumour immune response that abrogated tumour growth in syngeneic immunocompetent mice, but not in immunodeficient mice. Mechanistically, PI3Kβ inactivation in the PTEN-null setting led to reduced STAT3 signalling and increased the expression of immune stimulatory molecules, thereby promoting anti-tumour immune responses. Pharmacological PI3Kβ inhibition also elicited anti-tumour immunity and synergized with immunotherapy to inhibit tumour growth. Mice with complete responses to the combined treatment displayed immune memory and rejected tumours upon re-challenge. Our findings demonstrate a molecular mechanism linking PTEN loss and STAT3 activation in cancer and suggest that PI3Kβ controls immune escape in PTEN-null tumours, providing a rationale for combining PI3Kβ inhibitors with immunotherapy for the treatment of PTEN-deficient breast cancer. <<<
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6.
大勇 (2023-06-30 21:35):
#paper Dmitrieva-Posocco, O., Wong, A.C., Lundgren, P. et al. β-Hydroxybutyrate suppresses colorectal cancer. Nature 605, 160–165 (2022). https://doi.org/10.1038/s41586-022-04649-6 主要是讲述生酮饮食对小鼠结肠癌的抑制作用及可能的机制探讨,整篇文献降解较为精简,细节可以在文章中继续探索,生酮饮食对脂质、糖类和蛋白的代谢都会造成影响,从而导致结肠癌生长的抑制,酮类中的β羟丁酸可以通过Hcar2基因诱导Hopx的表达升高,从而抑制结肠癌进展。在生酮饮食研究中,其实还有其他研究表明生酮饮食会造成肿瘤的进展而非抑制,并且生酮饮食可能还会加速衰老和增加心血管疾病的风险,因此若非药用,日常不适宜进行尝试,目前在临床中没有太多的验证,而对于遗传代谢病中糖代谢异常的患者,生酮饮食则可能是他们目前最为稳妥的饮食方式,因为糖类可能对他们来说反而是毒药。
IF:50.500Q1 Nature, 2022-05. DOI: 10.1038/s41586-022-04649-6 PMID: 35477756
Abstract:
Colorectal cancer (CRC) is among the most frequent forms of cancer, and new strategies for its prevention and therapy are urgently needed. Here we identify a metabolite signalling pathway that … >>>
Colorectal cancer (CRC) is among the most frequent forms of cancer, and new strategies for its prevention and therapy are urgently needed. Here we identify a metabolite signalling pathway that provides actionable insights towards this goal. We perform a dietary screen in autochthonous animal models of CRC and find that ketogenic diets exhibit a strong tumour-inhibitory effect. These properties of ketogenic diets are recapitulated by the ketone body β-hydroxybutyrate (BHB), which reduces the proliferation of colonic crypt cells and potently suppresses intestinal tumour growth. We find that BHB acts through the surface receptor Hcar2 and induces the transcriptional regulator Hopx, thereby altering gene expression and inhibiting cell proliferation. Cancer organoid assays and single-cell RNA sequencing of biopsies from patients with CRC provide evidence that elevated BHB levels and active HOPX are associated with reduced intestinal epithelial proliferation in humans. This study thus identifies a BHB-triggered pathway regulating intestinal tumorigenesis and indicates that oral or systemic interventions with a single metabolite may complement current prevention and treatment strategies for CRC. <<<
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7.
大勇 (2023-05-31 22:11):
#paper doi: https://doi.org/10.1038/s41586-022-05443-0 Kim, R., Hashimoto, A., Markosyan, N. et al. Ferroptosis of tumour neutrophils causes immune suppression in cancer. Nature 612, 338–346 (2022). 该文章主要是对肿瘤相关中性粒,也叫做髓源性抑制细胞(PMN-MDSC)在抗肿瘤免疫中的作用进行了研究,PMN-MDSC中所产生的铁死亡相关脂质代谢产物,可以通过抑制T细胞等的增殖从而抑制肿瘤进展和免疫检查点抑制剂治疗疗效。
IF:50.500Q1 Nature, 2022-12. DOI: 10.1038/s41586-022-05443-0 PMID: 36385526
Abstract:
Ferroptosis is a non-apoptotic form of regulated cell death that is triggered by the discoordination of regulatory redox mechanisms culminating in massive peroxidation of polyunsaturated phospholipids. Ferroptosis inducers have shown … >>>
Ferroptosis is a non-apoptotic form of regulated cell death that is triggered by the discoordination of regulatory redox mechanisms culminating in massive peroxidation of polyunsaturated phospholipids. Ferroptosis inducers have shown considerable effectiveness in killing tumour cells in vitro, yet there has been no obvious success in experimental animal models, with the notable exception of immunodeficient mice. This suggests that the effect of ferroptosis on immune cells remains poorly understood. Pathologically activated neutrophils (PMNs), termed myeloid-derived suppressor cells (PMN-MDSCs), are major negative regulators of anti-tumour immunity. Here we found that PMN-MDSCs in the tumour microenvironment spontaneously die by ferroptosis. Although decreasing the presence of PMN-MDSCs, ferroptosis induces the release of oxygenated lipids and limits the activity of human and mouse T cells. In immunocompetent mice, genetic and pharmacological inhibition of ferroptosis abrogates suppressive activity of PMN-MDSCs, reduces tumour progression and synergizes with immune checkpoint blockade to suppress the tumour growth. By contrast, induction of ferroptosis in immunocompetent mice promotes tumour growth. Thus, ferroptosis is a unique and targetable immunosuppressive mechanism of PMN-MDSCs in the tumour microenvironment that can be pharmacologically modulated to limit tumour progression. <<<
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8.
大勇 (2023-04-30 21:33):
#paper Tim-4+ cavity-resident macrophages impair anti-tumor CD8+ T cell immunity. Cancer Cell. 2021 Jul 12;39(7):973-988.e9. doi: 10.1016/j.ccell.2021.05.006. Epub 2021 Jun 10. PMID: 34115989; PMCID: PMC9115604.文章的概念比较新颖,探究了腹腔转移肿瘤对免疫检查点抑制剂耐药的相关机制,找到了体腔驻留的TIM4阳性的巨噬细胞在其中发挥的影响,利用TIM4阳性的巨噬细胞与CD8+CD39+T细胞的相互作用,阐释了体腔驻留巨噬细胞可以抑制CD8T细胞的功能,并且TIM4单抗可以与PD1单抗联合用药治疗肿瘤,提高疗效。
IF:48.800Q1 Cancer cell, 2021-07-12. DOI: 10.1016/j.ccell.2021.05.006 PMID: 34115989
Abstract:
Immune checkpoint blockade (ICB) has been a remarkable clinical advance for cancer; however, the majority of patients do not respond to ICB therapy. We show that metastatic disease in the … >>>
Immune checkpoint blockade (ICB) has been a remarkable clinical advance for cancer; however, the majority of patients do not respond to ICB therapy. We show that metastatic disease in the pleural and peritoneal cavities is associated with poor clinical outcomes after ICB therapy. Cavity-resident macrophages express high levels of Tim-4, a receptor for phosphatidylserine (PS), and this is associated with reduced numbers of CD8 T cells with tumor-reactive features in pleural effusions and peritoneal ascites from patients with cancer. We mechanistically demonstrate that viable and cytotoxic anti-tumor CD8 T cells upregulate PS and this renders them susceptible to sequestration away from tumor targets and proliferation suppression by Tim-4 macrophages. Tim-4 blockade abrogates this sequestration and proliferation suppression and enhances anti-tumor efficacy in models of anti-PD-1 therapy and adoptive T cell therapy in mice. Thus, Tim-4 cavity-resident macrophages limit the efficacy of immunotherapies in these microenvironments. <<<
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9.
大勇 (2023-03-31 21:39):
#paper Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer. Immunity. 2022 Mar 8;55(3):527-541.e5. doi: 10.1016/j.immuni.2022.02.001. Epub 2022 Feb 28. PMID: 35231421这篇文献主要通过空间转录组的数据和计算机成像,给我们展示了肿瘤组织中三级淋巴结构的微环境细胞图谱,发现B细胞聚集区以及B细胞抗原刺激的过程。并且CXCL12的成纤维细胞可以促进B细胞的扩散和发挥抗体介导的肿瘤ADCC的作用。
IF:25.500Q1 Immunity, 2022-03-08. DOI: 10.1016/j.immuni.2022.02.001 PMID: 35231421
Abstract:
The presence of intratumoral tertiary lymphoid structures (TLS) is associated with positive clinical outcomes and responses to immunotherapy in cancer. Here, we used spatial transcriptomics to examine the nature of … >>>
The presence of intratumoral tertiary lymphoid structures (TLS) is associated with positive clinical outcomes and responses to immunotherapy in cancer. Here, we used spatial transcriptomics to examine the nature of B cell responses within TLS in renal cell carcinoma (RCC). B cells were enriched in TLS, and therein, we could identify all B cell maturation stages toward plasma cell (PC) formation. B cell repertoire analysis revealed clonal diversification, selection, expansion in TLS, and the presence of fully mature clonotypes at distance. In TLS+ tumors, IgG- and IgA-producing PCs disseminated into the tumor beds along fibroblastic tracks. TLS+ tumors exhibited high frequencies of IgG-producing PCs and IgG-stained and apoptotic malignant cells, suggestive of anti-tumor effector activity. Therapeutic responses and progression-free survival correlated with IgG-stained tumor cells in RCC patients treated with immune checkpoint inhibitors. Thus, intratumoral TLS sustains B cell maturation and antibody production that is associated with response to immunotherapy, potentially via direct anti-tumor effects. <<<
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10.
大勇 (2023-02-28 23:35):
#paper  CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4. Cancer Cell. 2022 Apr 11;40(4):365-378.e6. doi: 10.1016/j.ccell.2022.02.003. Epub 2022 Feb 24. 这篇文献主要讲述了CD8+T细胞通过分泌内源性的IFNγ,可以作用与肿瘤细胞,引起ACSL4的表达升高,与花生四烯酸协同促进肿瘤的脂质代谢并诱导肿瘤细胞铁死亡,在此过程中,可以促进肿瘤对免疫检查点抑制剂的疗效。
IF:48.800Q1 Cancer cell, 2022-04-11. DOI: 10.1016/j.ccell.2022.02.003 PMID: 35216678
Abstract:
Tumor cell intrinsic ferroptosis-initiating mechanisms are unknown. Here, we discover that T cell-derived interferon (IFN)γ in combination with arachidonic acid (AA) induces immunogenic tumor ferroptosis, serving as a mode of … >>>
Tumor cell intrinsic ferroptosis-initiating mechanisms are unknown. Here, we discover that T cell-derived interferon (IFN)γ in combination with arachidonic acid (AA) induces immunogenic tumor ferroptosis, serving as a mode of action for CD8 T cell (CTL)-mediated tumor killing. Mechanistically, IFNγ stimulates ACSL4 and alters tumor cell lipid pattern, thereby increasing incorporations of AA into C16 and C18 acyl chain-containing phospholipids. Palmitoleic acid and oleic acid, two common C16 and C18 fatty acids in blood, promote ACSL4-dependent tumor ferroptosis induced by IFNγ plus AA. Moreover, tumor ACSL4 deficiency accelerates tumor progression. Low-dose AA enhances tumor ferroptosis and elevates spontaneous and immune checkpoint blockade (ICB)-induced anti-tumor immunity. Clinically, tumor ACSL4 correlates with T cell signatures and improved survival in ICB-treated cancer patients. Thus, IFNγ signaling paired with selective fatty acids is a natural tumor ferroptosis-promoting mechanism and a mode of action of CTLs. Targeting the ACSL4 pathway is a potential anti-cancer approach. <<<
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11.
大勇 (2023-01-31 21:58):
#paper # Methionine deficiency facilitates antitumour immunity by altering m6A methylation of immune checkpoint transcripts. Gut. 2022 Jul 8:gutjnl-2022-326928. doi: 10.1136/gutjnl-2022-326928. 这篇文献主要讲述了甲硫氨酸(蛋氨酸)的缺乏饮食可以抑制肿瘤的增殖,而这个过程依赖于PDL1和VISTA的m6A甲基化水平的改变,甲硫氨酸缺乏所引起的甲基代谢的异常,会使得YDHDF1对PDL1和VISTA mRNA的m6A甲基化水平下降,从而增强了它们的翻译和表达,最终促进了T细胞的浸润和PDL1抑制剂治疗的疗效。
IF:23.000Q1 Gut, 2023-03. DOI: 10.1136/gutjnl-2022-326928 PMID: 35803704
Abstract:
OBJECTIVE: Methionine metabolism is involved in a myriad of cellular functions, including methylation reactions and redox maintenance. Nevertheless, it remains unclear whether methionine metabolism, RNA methylation and antitumour immunity are … >>>
OBJECTIVE: Methionine metabolism is involved in a myriad of cellular functions, including methylation reactions and redox maintenance. Nevertheless, it remains unclear whether methionine metabolism, RNA methylation and antitumour immunity are molecularly intertwined.DESIGN: The antitumour immunity effect of methionine-restricted diet (MRD) feeding was assessed in murine models. The mechanisms of methionine and YTH domain-containing family protein 1 (YTHDF1) in tumour immune escape were determined in vitro and in vivo. The synergistic effects of MRD or YTHDF1 depletion with PD-1 blockade were also investigated.RESULTS: We found that dietary methionine restriction reduced tumour growth and enhanced antitumour immunity by increasing the number and cytotoxicity of tumour-infiltrating CD8+ T cells in different mouse models. Mechanistically, the S-adenosylmethionine derived from methionine metabolism promoted the N6-methyladenosine (m6A) methylation and translation of immune checkpoints, including PD-L1 and V-domain Ig suppressor of T cell activation (VISTA), in tumour cells. Furthermore, MRD or m6A-specific binding protein YTHDF1 depletion inhibited tumour growth by restoring the infiltration of CD8+ T cells, and synergised with PD-1 blockade for better tumour control. Clinically, YTHDF1 expression correlated with poor prognosis and immunotherapy outcomes for cancer patients.CONCLUSIONS: Methionine and YTHDF1 play a critical role in anticancer immunity through regulating the functions of T cells. Targeting methionine metabolism or YTHDF1 could be a potential new strategy for cancer immunotherapy. <<<
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大勇 (2022-12-31 23:13):
# paper Aversive memory formation in humans involves an amygdala-hippocampus phase code,2022,nature communication,https://doi.org/10.1038/s41467-022-33828-2 我们对于情绪性事件一般都会有一个更深刻的记忆,这一机制被认为是由于杏仁核调节了海马活动而导致的,然而这两个脑区间是如何交互的,其又是通过怎样一种神经动态的机制来影响记忆的并不清楚,本文作者利用颅内记录,发现成功编码的情绪记忆会伴随杏仁核theta相位与海马gamma振荡及神经元放电的耦合,随后记得和不记得的情绪刺激之间的相位差转化为一个时间段,形成了杏仁核和下游海马伽马之间的一致性滞后。这些结果揭示了一种机制,杏仁核 theta 相位协调瞬态杏仁核-海马伽马相干性以促进厌恶记忆编码。杏仁核可以传递情绪记忆的内容到其他脑区从而调节其他认知功能。
IF:14.700Q1 Nature communications, 2022-10-27. DOI: 10.1038/s41467-022-33828-2 PMID: 36302909
Abstract:
Memory for aversive events is central to survival but can become maladaptive in psychiatric disorders. Memory enhancement for emotional events is thought to depend on amygdala modulation of hippocampal activity. … >>>
Memory for aversive events is central to survival but can become maladaptive in psychiatric disorders. Memory enhancement for emotional events is thought to depend on amygdala modulation of hippocampal activity. However, the neural dynamics of amygdala-hippocampal communication during emotional memory encoding remain unknown. Using simultaneous intracranial recordings from both structures in human patients, here we show that successful emotional memory encoding depends on the amygdala theta phase to which hippocampal gamma activity and neuronal firing couple. The phase difference between subsequently remembered vs. not-remembered emotional stimuli translates to a time period that enables lagged coherence between amygdala and downstream hippocampal gamma. These results reveal a mechanism whereby amygdala theta phase coordinates transient amygdala -hippocampal gamma coherence to facilitate aversive memory encoding. Pacing of lagged gamma coherence via amygdala theta phase may represent a general mechanism through which the amygdala relays emotional content to distant brain regions to modulate other aspects of cognition, such as attention and decision-making. <<<
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