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Hana Starobova, Mercedes Monteleone, Christelle Adolphe, Lena Batoon, Cheyenne J. Sandrock, Bryan Tay, Jennifer R. Deuis, Alexandra V. Smith, Alexander Mueller, Evelyn Israel Nadar, Grace Pamo Lawrence, Amanda Mayor, Elissa Tolson, Jean-Pierre Levesque, Allison R. Pettit, Brandon J. Wainwright, Kate Schroder, Irina Vetter
Starobova et al. demonstrate that vincristine-induced peripheral neuropathy (VIPN) is driven by activation of the NLRP3 inflammasome and release of IL-1β. Moreover, inhibition of NLRP3-mediated IL-1β release prevents VIPN in a murine model without affecting chemotherapy efficacy.
Kristen E. Pauken, Osmaan Shahid, Kaitlyn A. Lagattuta, Kelly M. Mahuron, Jacob M. Luber, Margaret M. Lowe, Linglin Huang, Conor Delaney, Jaclyn M. Long, Megan E. Fung, Kathleen Newcomer, Katy K. Tsai, Melissa Chow, Samantha Guinn, Juhi R. Kuchroo, Kelly P. Burke, Jason M. Schenkel, Michael D. Rosenblum, Adil I. Daud, Arlene H. Sharpe, Meromit Singer
Using single-cell RNA sequencing and TCR sequencing, Pauken et al. detect CD8+ T cell clones shared between blood and tumor in mice or melanoma patients, characterize matching clones in blood and tumor, and identify potential biomarkers for their isolation in blood.
Brief Definitive Report
Liliana E. Lucca, Pierre-Paul Axisa, Benjamin Lu, Brian Harnett, Shlomit Jessel, Le Zhang, Khadir Raddassi, Lin Zhang, Kelly Olino, James Clune, Meromit Singer, Harriet M. Kluger, David A. Hafler
Combining transcriptomic and TCRαβ repertoire analysis of circulating and tumor-infiltrating CD8 T cells from patients with metastatic melanoma, Lucca et al. identify a blood-based population with effector properties that reflect those of clonally related tumor-resident T cells.
Kevin D. Rynearson, Moorthi Ponnusamy, Olga Prikhodko, Yuhuan Xie, Can Zhang, Phuong Nguyen, Brenda Hug, Mariko Sawa, Ann Becker, Brian Spencer, Jazmin Florio, Michael Mante, Bahar Salehi, Carlos Arias, Douglas Galasko, Brian P. Head, Graham Johnson, Jiunn H. Lin, Steven K. Duddy, Robert A. Rissman, William C. Mobley, Gopal Thinakaran, Rudolph E. Tanzi, Steven L. Wagner
GSMs preferentially attenuate levels of the aggregation-prone Aβ42 peptide by binding to the γ-secretase enzyme and altering exopeptidase-like processing. Rynearson et al. demonstrate the ability of an advanced-stage GSM to robustly attenuate Aβ42 levels across species and modify pathogenesis in a transgenic cerebral amyloidosis mouse model.
Nina Le Bert, Hannah E. Clapham, Anthony T. Tan, Wan Ni Chia, Christine Y.L. Tham, Jane M. Lim, Kamini Kunasegaran, Linda Wei Lin Tan, Charles-Antoine Dutertre, Nivedita Shankar, Joey M.E. Lim, Louisa Jin Sun, Marina Zahari, Zaw Myo Tun, Vishakha Kumar, Beng Lee Lim, Siew Hoon Lim, Adeline Chia, Yee-Joo Tan, Paul Anantharajah Tambyah, Shirin Kalimuddin, David Lye, Jenny G.H. Low, Lin-Fa Wang, Wei Yee Wan, Li Yang Hsu, Antonio Bertoletti, Clarence C. Tam
By using a rapid whole-blood T cell activation assay measuring cytokines released by SARS-CoV-2–specific T cells, Le Bert et al. show that individuals who clear SARS-CoV-2 infection without symptoms mount a highly functional virus-specific cellular immune response.
Brief Definitive Report
Siddharth Krishnan, Kelly Wemyss, Ian E. Prise, Flora A. McClure, Conor O’Boyle, Hayley M. Bridgeman, Tovah N. Shaw, John R. Grainger, Joanne E. Konkel
Krishnan et al. outline a novel pathway of myeloid cell development in healthy gingiva. They identify HSPCs in noninflamed gingiva tissue, which support the generation of a proportion of the innate immune cells that police this barrier site.
Celia Rupérez, Gemma Ferrer-Curriu, Aina Cervera-Barea, Laura Florit, Mariona Guitart-Mampel, Gloria Garrabou, Mònica Zamora, Fàtima Crispi, Joaquim Fernandez-Solà, Josep Lupón, Antoni Bayes-Genis, Francesc Villarroya, Anna Planavila
Rupérez et al. report the discovery of the protein Metrnβ as a new cardiokine with cardioprotective actions. They established that the heart produces Metrnβ, which in turn protects against cardiac hypertrophy. Metrnβ is also a new prognostic biomarker in heart failure patients.

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