Journal of Experimental Medicine最新文献

Kazuyo Moro: Building relationships is essential for gaining both speed and opportunities in research.

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-03-03 Epub Date: 2024-12-04 DOI: 10.1084/jem.20242176

Montserrat Cols

引用次数: 0

Altered X-chromosome inactivation of the TLR7/8 locus and heterogeneity of pDCs in systemic sclerosis.

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-03-03 Epub Date: 2024-12-13 DOI: 10.1084/jem.20231809

Yong Du, Bérénice Faz-Lopez, Marie Dominique Ah Kioon, Claire Cenac, Michael Pierides, Kimberly S Lakin, Robert F Spiera, Julie Chaumeil, Marie-Elise Truchetet, Jessica K Gordon, Jean-Charles Guéry, Franck J Barrat

{"title":"Altered X-chromosome inactivation of the TLR7/8 locus and heterogeneity of pDCs in systemic sclerosis.","authors":"Yong Du, Bérénice Faz-Lopez, Marie Dominique Ah Kioon, Claire Cenac, Michael Pierides, Kimberly S Lakin, Robert F Spiera, Julie Chaumeil, Marie-Elise Truchetet, Jessica K Gordon, Jean-Charles Guéry, Franck J Barrat","doi":"10.1084/jem.20231809","DOIUrl":"10.1084/jem.20231809","url":null,"abstract":"Systemic sclerosis (SSc) is an autoimmune disease that has a strong female predominance. Both the X-linked TLR7 and TLR8 can induce type I IFN (IFN-I) by plasmacytoid DCs (pDCs), which can promote fibrosis. We identified five subclusters of pDCs, including ISGhigh clusters that were over-represented in SSc patients. We observed that both TLR7 and TLR8 genes escape from X chromosome inactivation (XCI) at higher frequency in pDCs of SSc patients, which was associated with changes in TLR7 protein profile. Combined DNA/RNA FISH analysis revealed that the TLR7/8 locus is preferentially located outside of the inactive X (Xi) territory when TLR7 is expressed, suggesting that higher-order loop formation is linked to TLR7/8 expression from the Xi. Furthermore, the expression levels of XIST and the transcriptional repressor SPEN were reduced in SSc pDCs. Hence, our data revealed the heterogeneity of pDCs in SSc and suggested that altered XCI at the TLR7/8 locus may contribute to the chronic IFN-I activity of pDCs in female SSc patients.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"222 3","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11639950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Autocrine TGF-β1 drives tissue-specific differentiation and function of resident NK cells.

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-03-03 Epub Date: 2024-12-18 DOI: 10.1084/jem.20240930

Colin Sparano, Darío Solís-Sayago, Nathan Sébastien Zangger, Lukas Rindlisbacher, Hannah Van Hove, Marijne Vermeer, Frederike Westermann, Caroline Mussak, Elisa Rallo, Stanislav Dergun, Gioana Litscher, Yishu Xu, Mitchell Bijnen, Christin Friedrich, Melanie Greter, Vanda Juranić Lisnić, Burkhard Becher, Georg Gasteiger, Annette Oxenius, Sonia Tugues

{"title":"Autocrine TGF-β1 drives tissue-specific differentiation and function of resident NK cells.","authors":"Colin Sparano, Darío Solís-Sayago, Nathan Sébastien Zangger, Lukas Rindlisbacher, Hannah Van Hove, Marijne Vermeer, Frederike Westermann, Caroline Mussak, Elisa Rallo, Stanislav Dergun, Gioana Litscher, Yishu Xu, Mitchell Bijnen, Christin Friedrich, Melanie Greter, Vanda Juranić Lisnić, Burkhard Becher, Georg Gasteiger, Annette Oxenius, Sonia Tugues","doi":"10.1084/jem.20240930","DOIUrl":"https://doi.org/10.1084/jem.20240930","url":null,"abstract":"Group 1 innate lymphoid cells (ILCs) encompass NK cells and ILC1s, which have non-redundant roles in host protection against pathogens and cancer. Despite their circulating nature, NK cells can establish residency in selected tissues during ontogeny, forming a distinct functional subset. The mechanisms that initiate, maintain, and regulate the conversion of NK cells into tissue-resident NK (trNK) cells are currently not well understood. Here, we identify autocrine transforming growth factor-β (TGF-β) as a cell-autonomous driver for NK cell tissue residency across multiple glandular tissues during development. Cell-intrinsic production of TGF-β was continuously required for the maintenance of trNK cells and synergized with Hobit to enhance cytotoxic function. Whereas autocrine TGF-β was redundant in tumors, our study revealed that NK cell-derived TGF-β allowed the expansion of cytotoxic trNK cells during local infection with murine cytomegalovirus (MCMV) and contributed to viral control in the salivary gland. Collectively, our findings reveal tissue-specific regulation of trNK cell differentiation and function by autocrine TGF-β1, which is relevant for antiviral immunity.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"222 3","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanosensing regulates pDC activation in the skin through NRF2 activation.

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-03-03 Epub Date: 2024-12-13 DOI: 10.1084/jem.20240852

Vidyanath Chaudhary, Bikash Mishra, Marie Dominique Ah Kioon, Yong Du, Lionel B Ivashkiv, Mary K Crow, Franck J Barrat

{"title":"Mechanosensing regulates pDC activation in the skin through NRF2 activation.","authors":"Vidyanath Chaudhary, Bikash Mishra, Marie Dominique Ah Kioon, Yong Du, Lionel B Ivashkiv, Mary K Crow, Franck J Barrat","doi":"10.1084/jem.20240852","DOIUrl":"10.1084/jem.20240852","url":null,"abstract":"Plasmacytoid DCs (pDCs) infiltrate the skin, chronically produce type I interferon (IFN-I), and promote skin lesions and fibrosis in autoimmune patients. However, what controls their activation in the skin is unknown. Here, we report that increased stiffness inhibits the production of IFN-I by pDCs. Mechanistically, mechanosensing activates stress pathways including NRF2, which induces the pentose phosphate pathway and reduces pyruvate levels, a product necessary for pDC responses. Modulating NRF2 activity in vivo controlled the pDC response, leading to resolution or chronic induction of IFN-I in the skin. In systemic sclerosis (SSc) patients, although NRF2 was induced in skin-infiltrating pDCs, as compared with blood pDCs, the IFN response was maintained. We observed that CXCL4, a profibrotic chemokine elevated in fibrotic skin, was able to overcome stiffness-mediated IFN-I inhibition, allowing chronic IFN-I responses by pDCs in the skin. Hence, these data identify a novel regulatory mechanism exerted by the skin microenvironment and identify points of dysregulation of this mechanism in patients with skin inflammation and fibrosis.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"222 3","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11639951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CCDC134 controls TLR biogenesis through the ER chaperone Gp96.

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-03-03 Epub Date: 2024-12-10 DOI: 10.1084/jem.20240825

Léa Bernaleau, Michaela Drobek, Fenja Blank, Philipp Walch, Maeva Delacrétaz, Ales Drobek, Marta Monguió-Tortajada, Petr Broz, Olivia Majer, Manuele Rebsamen

{"title":"CCDC134 controls TLR biogenesis through the ER chaperone Gp96.","authors":"Léa Bernaleau, Michaela Drobek, Fenja Blank, Philipp Walch, Maeva Delacrétaz, Ales Drobek, Marta Monguió-Tortajada, Petr Broz, Olivia Majer, Manuele Rebsamen","doi":"10.1084/jem.20240825","DOIUrl":"10.1084/jem.20240825","url":null,"abstract":"Toll-like receptors (TLRs) are central to initiate immune responses against invading pathogens. To ensure host defense while avoiding aberrant activation leading to pathogenic inflammation and autoimmune diseases, TLRs are tightly controlled by multilevel regulatory mechanisms. Through a loss-of-function genetic screen in a reporter cell line engineered to undergo cell death upon TLR7-induced IRF5 activation, we identified here CCDC134 as an essential factor for TLR responses. CCDC134 deficiency impaired endolysosomal TLR-induced NF-κB, MAPK, and IRF5 activation, as well as downstream production of proinflammatory cytokines and type I interferons. We further demonstrated that CCDC134 is an endoplasmic reticulum (ER)-resident interactor of Gp96 (HSP90B1/Grp94), an ER chaperone essential for folding and trafficking of plasma membrane and endolysosomal TLRs. CCDC134 controlled Gp96 stability as its loss led to Gp96 hyperglycosylation and ER-associated protein degradation (ERAD)-mediated clearance. Accordingly, CCDC134 deficiency impaired the folding, maturation, and trafficking of TLRs, resulting in blunted inflammatory responses upon stimulation. Altogether, this study reveals CCDC134 as a central regulator of the chaperone Gp96, thereby controlling TLR biogenesis and responses.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"222 3","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dual role of vascular endothelial growth factor-C in post-stroke recovery.

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-02-03 Epub Date: 2024-12-12 DOI: 10.1084/jem.20231816

Yun Hwa Choi, Martin Hsu, Collin Laaker, Jenna Port, Kristóf G Kovács, Melinda Herbath, Heeyoon Yang, Peter Cismaru, Alexis M Johnson, Bailey Spellman, Kelsey Wigand, Matyas Sandor, Zsuzsanna Fabry

{"title":"Dual role of vascular endothelial growth factor-C in post-stroke recovery.","authors":"Yun Hwa Choi, Martin Hsu, Collin Laaker, Jenna Port, Kristóf G Kovács, Melinda Herbath, Heeyoon Yang, Peter Cismaru, Alexis M Johnson, Bailey Spellman, Kelsey Wigand, Matyas Sandor, Zsuzsanna Fabry","doi":"10.1084/jem.20231816","DOIUrl":"10.1084/jem.20231816","url":null,"abstract":"Cerebrospinal fluid (CSF), antigens, and antigen-presenting cells drain from the central nervous system (CNS) into lymphatic vessels near the cribriform plate and dura, yet the role of these vessels during stroke is unclear. Using a mouse model of ischemic stroke, transient middle cerebral artery occlusion (tMCAO), we demonstrate stroke-induced lymphangiogenesis near the cribriform plate, peaking at day 7 and regressing by day 14. Lymphangiogenesis is restricted to the cribriform plate and deep cervical lymph nodes and is regulated by VEGF-C/VEGFR-3 signaling. The use of a VEGFR-3 inhibitor prevented lymphangiogenesis and led to improved stroke outcomes at earlier time points, with no effects at later time points. VEGF-C delivery after tMCAO did not further increase post-stroke lymphangiogenesis, but instead induced larger brain infarcts. Our data support the damaging role of VEGF-C acutely and a pro-angiogenic role chronically. This nuanced understanding of VEGFR-3 and VEGF-C in stroke pathology advises caution regarding therapeutic VEGF-C use in stroke.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"222 2","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity.

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-02-03 Epub Date: 2024-12-16 DOI: 10.1084/jem.20241413

Fahd Al Qureshah, Jérémie Le Pen, Nicole A de Weerd, Marcela Moncada-Velez, Marie Materna, Daniel C Lin, Baptiste Milisavljevic, Fernanda Vianna, Lucy Bizien, Lazaro Lorenzo, Marc Lecuit, Jean-David Pommier, Sevgi Keles, Tayfun Ozcelik, Sigifredo Pedraza-Sanchez, Nicolas de Prost, Loubna El Zein, Hassan Hammoud, Lisa F P Ng, Rabih Halwani, Narjes Saheb Sharif-Askari, Yu Lung Lau, Anthony R Tam, Neha Singh, Sagar Bhattad, Yackov Berkun, Wasun Chantratita, Raúl Aguilar-López, Mohammad Shahrooei, Laurent Abel, Paul Bastard, Emmanuelle Jouanguy, Vivien Béziat, Peng Zhang, Charles M Rice, Aurélie Cobat, Shen-Ying Zhang, Paul J Hertzog, Jean-Laurent Casanova, Qian Zhang

{"title":"A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity.","authors":"Fahd Al Qureshah, Jérémie Le Pen, Nicole A de Weerd, Marcela Moncada-Velez, Marie Materna, Daniel C Lin, Baptiste Milisavljevic, Fernanda Vianna, Lucy Bizien, Lazaro Lorenzo, Marc Lecuit, Jean-David Pommier, Sevgi Keles, Tayfun Ozcelik, Sigifredo Pedraza-Sanchez, Nicolas de Prost, Loubna El Zein, Hassan Hammoud, Lisa F P Ng, Rabih Halwani, Narjes Saheb Sharif-Askari, Yu Lung Lau, Anthony R Tam, Neha Singh, Sagar Bhattad, Yackov Berkun, Wasun Chantratita, Raúl Aguilar-López, Mohammad Shahrooei, Laurent Abel, Paul Bastard, Emmanuelle Jouanguy, Vivien Béziat, Peng Zhang, Charles M Rice, Aurélie Cobat, Shen-Ying Zhang, Paul J Hertzog, Jean-Laurent Casanova, Qian Zhang","doi":"10.1084/jem.20241413","DOIUrl":"10.1084/jem.20241413","url":null,"abstract":"Autosomal recessive deficiency of the IFNAR1 or IFNAR2 chain of the human type I IFN receptor abolishes cellular responses to IFN-α, -β, and -ω, underlies severe viral diseases, and is globally very rare, except for IFNAR1 and IFNAR2 deficiency in Western Polynesia and the Arctic, respectively. We report 11 human IFNAR1 alleles, the products of which impair but do not abolish responses to IFN-α and -ω without affecting responses to IFN-β. Ten of these alleles are rare in all populations studied, but the remaining allele (P335del) is common in Southern China (minor allele frequency ≈2%). Cells heterozygous for these variants display a dominant phenotype in vitro with impaired responses to IFN-α and -ω, but not -β, and viral susceptibility. Negative dominance, rather than haploinsufficiency, accounts for this dominance. Patients heterozygous for these variants are prone to viral diseases, attesting to both the dominance of these variants clinically and the importance of IFN-α and -ω for protective immunity against some viruses.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"222 2","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cindy Ma: Science is often not black and white, and the answer usually lies in the grey.

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-02-03 Epub Date: 2024-12-05 DOI: 10.1084/jem.20242177

Montserrat Cols

引用次数: 0

Identification of α-galactosylceramide as an endogenous mammalian antigen for iNKT cells.

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-02-03 Epub Date: 2024-12-20 DOI: 10.1084/jem.20240728

Yuki Hosono, Noriyuki Tomiyasu, Hayato Kasai, Eri Ishikawa, Masatomo Takahashi, Akihiro Imamura, Hideharu Ishida, Federica Compostella, Hiroshi Kida, Atsushi Kumanogoh, Takeshi Bamba, Yoshihiro Izumi, Sho Yamasaki

{"title":"Identification of α-galactosylceramide as an endogenous mammalian antigen for iNKT cells.","authors":"Yuki Hosono, Noriyuki Tomiyasu, Hayato Kasai, Eri Ishikawa, Masatomo Takahashi, Akihiro Imamura, Hideharu Ishida, Federica Compostella, Hiroshi Kida, Atsushi Kumanogoh, Takeshi Bamba, Yoshihiro Izumi, Sho Yamasaki","doi":"10.1084/jem.20240728","DOIUrl":"https://doi.org/10.1084/jem.20240728","url":null,"abstract":"Invariant natural killer T (iNKT) cells are unconventional T cells recognizing lipid antigens in a CD1d-restricted manner. Among these lipid antigens, α-galactosylceramide (α-GalCer), which was originally identified in marine sponges, is the most potent antigen. Although the presence of α-anomeric hexosylceramide and microbiota-derived branched α-GalCer is reported, antigenic α-GalCer has not been identified in mammals. Here, we developed a high-resolution separation and detection system, supercritical fluid chromatography tandem mass spectrometry (SFC/MS/MS), that can discriminate hexosylceramide diastereomers (α-GalCer, α-GlcCer, β-GalCer, or β-GlcCer). The B16 melanoma tumor cell line does not activate iNKT cells; however, ectopic expression of CD1d was sufficient to activate iNKT cells without adding antigens. B16 melanoma was unlikely to generate iNKT cell antigens; instead, antigen activity was detected in cell culture serum. Activity-based purification and SFC/MS/MS identified dihydrosphingosine-based saturated α-GalCer as an antigenic component in serum, bile, and lymphoid tissues. These results show the first evidence for the presence of potent antigenic α-GalCer in mammals.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"222 2","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer. 缺氧与肺癌患者对免疫检查点抑制剂的获得性抵抗有关。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-01-06 Epub Date: 2024-11-25 DOI: 10.1084/jem.20231106

Camila Robles-Oteíza, Katherine Hastings, Jungmin Choi, Isabelle Sirois, Arvind Ravi, Francisco Expósito, Fernando de Miguel, James R Knight, Francesc López-Giráldez, Hyejin Choi, Nicholas D Socci, Taha Merghoub, Mark Awad, Gad Getz, Justin Gainor, Matthew D Hellmann, Étienne Caron, Susan M Kaech, Katerina Politi

{"title":"Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer.","authors":"Camila Robles-Oteíza, Katherine Hastings, Jungmin Choi, Isabelle Sirois, Arvind Ravi, Francisco Expósito, Fernando de Miguel, James R Knight, Francesc López-Giráldez, Hyejin Choi, Nicholas D Socci, Taha Merghoub, Mark Awad, Gad Getz, Justin Gainor, Matthew D Hellmann, Étienne Caron, Susan M Kaech, Katerina Politi","doi":"10.1084/jem.20231106","DOIUrl":"10.1084/jem.20231106","url":null,"abstract":"Despite the established use of immune checkpoint inhibitors (ICIs) to treat non-small cell lung cancer (NSCLC), only a subset of patients benefit from treatment and ∼50% of patients whose tumors respond eventually develop acquired resistance (AR). To identify novel drivers of AR, we generated murine Msh2 knock-out (KO) lung tumors that initially responded but eventually developed AR to anti-PD-1, alone or in combination with anti-CTLA-4. Resistant tumors harbored decreased infiltrating T cells and reduced cancer cell-intrinsic MHC-I and MHC-II levels, yet remained responsive to IFNγ. Resistant tumors contained extensive regions of hypoxia, and a hypoxia signature derived from single-cell transcriptional profiling of resistant cancer cells was associated with decreased progression-free survival in a cohort of NSCLC patients treated with anti-PD-1/PD-L1 therapy. Targeting hypoxic tumor regions using a hypoxia-activated pro-drug delayed AR to ICIs in murine Msh2 KO tumors. Thus, this work provides a rationale for targeting tumor metabolic features, such as hypoxia, in combination with immune checkpoint inhibition.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"222 1","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0