Apr 25, 2024

Leading Edge

50th Anniversary

Immunology is for everyone
• The Cell editorial team
This “Focus on Immunology” issue brings Cell’s 50th anniversary celebrations straight to your lymph nodes! Special Leading Edge articles highlight the exciting past, present, and future of the increasingly interdisciplinary field of immunology.

From periphery to center stage: 50 years of advancements in innate immunity
• Susan Carpenter,
• Luke A.J. O’Neill
Open Access
Understanding of innate immunity has expanded enormously in recent history. In light of Cell's 50th anniversary, this review traces the development of the innate immunity field from the 1970s through today, highlighting how advances in knowledge now lead to therapeutic strategies.
Featured Article

Principles and therapeutic applications of adaptive immunity
• Hongbo Chi,
• Marion Pepper,
• Paul G. Thomas
Open Access
The processes of adaptive immunity are central to both health and disease. This review presents a comprehensive yet straightforward overview of lymphocyte biology, homing in on how understanding adaptive immunity holds the key to therapies and future discoveries.

Exploring new perspectives in immunology
• Ruslan Medzhitov,
• Akiko Iwasaki
Despite deep knowledge of how the immune system works, many questions remain difficult to answer within the current core framework of innate and adaptive immunity. This perspective highlights open questions where a change in the conceptual approach could be transformative for addressing persistent challenges to human health.

The plant immune system: From discovery to deployment
• Jonathan D.G. Jones,
• Brian J. Staskawicz,
• Jeffery L. Dangl
Open Access
Plant diseases significantly impact human and environmental health. This review encompasses the last 50 years of research in the plant immune system, an overview of the pathogen virulence proteins, and strategies for durable resistance.

Many paths lead to immunology
• Ana J. García-Sáez,
• Ana I. Domingos,
• J. Silvio Gutkind,
• Seema Mattoo,
• Peng Du
While some people pore over the textbook and train through the classics of the field, many scientists come to immunology when they discover it intersecting with their “first love” interests. Five of these “accidental immunologists” tell us how they found their way to a fascination with the immune system.

Creating connections when we talk about science
For Cell’s 50^th anniversary Focus on Immunology, scientific editor Cheri Sirois asked science communicator Liz Neeley, founding partner of Liminal and cofounder of Solving for Science, to discuss strategies for tackling technical complexity and for engaging effectively with broad audiences. A lightly edited transcript of their conversation is shared here.

Previews

A glycolytic metabolite that drives BRCA2 haploinsufficiency
• Peng Jiang
Many types of tumor cells alter metabolic pathways to meet their energy and biosynthetic demands for proliferation or stress adaptation. In this issue of Cell, Kong et al. find that the glycolytic metabolite methylglyoxal causes cancer-associated mutant single-base substitution features by inducing BRCA2 proteolysis, leading to functional haploinsufficiency of BRCA2.

Mapping the pancancer metastasis tumor microbiome
• Chi Chun Wong,
• Jun Yu
The landscape of the intratumoral microbiome in tumor metastases is largely unchartered. In this issue of Cell, Voest et al. profiled the tumor metastasis-associated microbiome in a pancancer cohort of 4,160 biopsies from 26 cancer types. This dataset offers a useful resource for understanding the role of the microbiome in metastatic cancers.

Articles

Generation of rat forebrain tissues in mice
• Jia Huang,
• Bingbing He,
• Xiali Yang,
• Xin Long,
• Yinghui Wei,
• Leijie Li,
• Min Tang,
• Yanxia Gao,
• Yuan Fang,
• Wenqin Ying,
• Zikang Wang,
• Chao Li,
• Yingsi Zhou,
• Shuaishuai Li,
• Linyu Shi,
• Seungwon Choi,
• Haibo Zhou,
• Fan Guo,
• Hui Yang,
• Jun Wu
An optimized screening platform streamlined the identification of mutations that supported the generation of rat forebrain tissue in mice via interspecies blastocyst complementation.

Functional sensory circuits built from neurons of two species
• Benjamin T. Throesch,
• Muhammad Khadeesh bin Imtiaz,
• Rodrigo Muñoz-Castañeda,
• Masahiro Sakurai,
• Andrea L. Hartzell,
• Kiely N. James,
• Alberto R. Rodriguez,
• Greg Martin,
• Giordano Lippi,
• Sergey Kupriyanov,
• Zhuhao Wu,
• Pavel Osten,
• Juan Carlos Izpisua Belmonte,
• Jun Wu,
• Kristin K. Baldwin
Generating brains from two different species via blastocyst complementation enables synchronous development of appropriate interspecies circuits. When host sensory neurons are disabled, donor neurons restore a primal odor-driven food-seeking behavior, showing that one species can sense and respond to the world through the cognate neurons of another.

Time-series reconstruction of the molecular architecture of human centriole assembly
• Marine H. Laporte,
• Davide Gambarotto,
• Éloïse Bertiaux,
• Lorène Bournonville,
• Vincent Louvel,
• José M. Nunes,
• Susanne Borgers,
• Virginie Hamel,
• Paul Guichard
Open Access
Expansion microscopy and time-series reconstructions enable elaboration of dynamic centriole assembly.

Short-distance vesicle transport via phase separation
• Hua Qiu,
• Xiandeng Wu,
• Xiaoli Ma,
• Shulin Li,
• Qixu Cai,
• Marcelo Ganzella,
• Liang Ge,
• Hong Zhang,
• Mingjie Zhang
Using the reconstituted presynaptic terminal local vesicle transport as a paradigm, Qiu and Wu et al. demonstrate that short-distance and directional vesicle transport can be achieved via regulated phase separation of vesicles with different protein condensates without involving molecular motors.

Flexible scaffold-based cheminformatics approach for polypharmacological drug design
• Zhangcheng Chen,
• Jing Yu,
• Huan Wang,
• Peiyu Xu,
• Luyu Fan,
• Fengxiu Sun,
• Sijie Huang,
• Pei Zhang,
• He Huang,
• Shuo Gu,
• Bowen Zhang,
• Yue Zhou,
• Xiaobo Wan,
• Gang Pei,
• H. Eric Xu,
• Jianjun Cheng,
• Sheng Wang
The flexible scaffold-based cheminformatics approach (FSCA) unlocks the potential of drug design to create polypharmacological drugs that open up treatment possibilities for complex brain disorders.

Positive selection CRISPR screens reveal a druggable pocket in an oligosaccharyltransferase required for inflammatory signaling to NF-κB
• Benjamin L. Lampson,
• Ana S. Ramίrez,
• Marta Baro,
• Lixia He,
• Mudra Hegde,
• Vidyasagar Koduri,
• Jamie L. Pfaff,
• Ruth E. Hanna,
• Julia Kowal,
• Nitin H. Shirole,
• Yanfeng He,
• John G. Doench,
• Joseph N. Contessa,
• Kaspar P. Locher,
• William G. Kaelin Jr.
Open Access
Innovative approaches identify druggable glycosylation processes that regulate TLR4-mediated activation of the pro-inflammatory transcription factor NF-κB.

NINJ1 mediates plasma membrane rupture by cutting and releasing membrane disks
• Liron David,
• Jazlyn P. Borges,
• L. Robert Hollingsworth,
• Allen Volchuk,
• Isabelle Jansen,
• Evelyn Garlick,
• Benjamin E. Steinberg,
• Hao Wu
Pyroptosis is a form of signaling-induced cell death characterized by plasma membrane rupture. This study suggests a “cookie cutter”-like mechanism for pyroptotic cell lysis in which oligomerization of the protein NINJ1 punches holes out of the plasma membrane and liberates “cookie”-like disks.

RNA genome packaging and capsid assembly of bluetongue virus visualized in host cells
• Xian Xia,
• Po-Yu Sung,
• Michael W. Martynowycz,
• Tamir Gonen,
• Polly Roy,
• Z. Hong Zhou
Integrated structural analyses captured a total of eleven assembly states of bluetongue virus (BTV), revealing insights into the mysterious RNA packaging and capsid assembly of dsRNA viruses.

The SPATA5-SPATA5L1 ATPase complex directs replisome proteostasis to ensure genome integrity
• Vidhya Krishnamoorthy,
• Martina Foglizzo,
• Robert L. Dilley,
• Angela Wu,
• Arindam Datta,
• Parul Dutta,
• Lisa J. Campbell,
• Oksana Degtjarik,
• Laura J. Musgrove,
• Antonio N. Calabrese,
• Elton Zeqiraj,
• Roger A. Greenberg
The 55LCC heterohexameric ATPase complex promotes replisome proteostasis to maintain replication fork progression and genome stability.

A glycolytic metabolite bypasses “two-hit” tumor suppression by BRCA2
• Li Ren Kong,
• Komal Gupta,
• Andy Jialun Wu,
• David Perera,
• Roland Ivanyi-Nagy,
• Syed Moiz Ahmed,
• Tuan Zea Tan,
• Shawn Lu-Wen Tan,
• Alessandra Fuddin,
• Elayanambi Sundaramoorthy,
• Grace Shiqing Goh,
• Regina Tong Xin Wong,
• Ana S.H. Costa,
• Callum Oddy,
• Hannan Wong,
• C. Pawan K. Patro,
• Yun Suen Kho,
• Xiao Zi Huang,
• Joan Choo,
• Mona Shehata,
• Soo Chin Lee,
• Boon Cher Goh,
• Christian Frezza,
• Jason J. Pitt,
• Ashok R. Venkitaraman
Open Access
Cells carrying a monoallelic germline BRCA2 mutation can bypass Knudson’s “two-hit” requirement to initiate tumorigenesis when the glycolytic metabolite methylglyoxal transiently disables BRCA2 function. Metabolic bypass of tumor suppressor activity may link metabolic reprogramming, metabolic disorders, or diet to early steps in carcinogenesis.

Cancer SLC6A6-mediated taurine uptake transactivates immune checkpoint genes and induces exhaustion in CD8⁺ T cells
• Tianyu Cao,
• Wenyao Zhang,
• Qi Wang,
• Chen Wang,
• Wanqi Ma,
• Cangang Zhang,
• Minghui Ge,
• Miaomiao Tian,
• Jia Yu,
• Anjun Jiao,
• Liang Wang,
• Manjiao Liu,
• Pei Wang,
• Zhiyu Guo,
• Yun Zhou,
• Shuyi Chen,
• Wen Yin,
• Jing Yi,
• Hao Guo,
• Hua Han,
• Baojun Zhang,
• Kaichun Wu,
• Daiming Fan,
• Xin Wang,
• Yongzhan Nie,
• Yuanyuan Lu,
• Xiaodi Zhao
Through SLC6A6-mediated taurine uptake, cancer cells become more aggressive and induce CD8⁺ T cell exhaustion by increasing ER stress and ATF4 transcription, resulting in immune evasion and tumor progression.

ITPRIPL1 binds CD3ε to impede T cell activation and enable tumor immune evasion
• Shouyan Deng,
• Yibo Zhang,
• Huanbin Wang,
• Wenhua Liang,
• Lu Xie,
• Ning Li,
• Yuan Fang,
• Yiting Wang,
• Jiayang Liu,
• Hao Chi,
• Yufan Sun,
• Rui Ye,
• Lishen Shan,
• Jiawei Shi,
• Zan Shen,
• Yonggang Wang,
• Shuhang Wang,
• Jean-Philippe Brosseau,
• Feng Wang,
• Grace Liu,
• Yingfei Quan,
• Jie Xu
An inhibitory ligand acts directly on CD3e to regulate T cell activation, and disruption of the interaction boosts tumor-specific T cell cytotoxicity to limit tumor growth.

Resources

Featured Article

A pan-cancer analysis of the microbiome in metastatic cancer
• Thomas W. Battaglia,
• Iris L. Mimpen,
• Joleen J.H. Traets,
• Arne van Hoeck,
• Laurien J. Zeverijn,
• Birgit S. Geurts,
• Gijs F. de Wit,
• Michaël Noë,
• Ingrid Hofland,
• Joris L. Vos,
• Sten Cornelissen,
• Maartje Alkemade,
• Annegien Broeks,
• Charlotte L. Zuur,
• Edwin Cuppen,
• Lodewyk Wessels,
• Joris van de Haar,
• Emile Voest
Open Access
Characterization of microbiome genomes at the species level in over 4,000 metastatic tumor biopsies identifies the distribution and diversity features of tumor-resident bacterial DNA at a pan-cancer scale, highlighting the associations between microbial community dynamics and tumor immunity and immunotherapy efficacy.

A genome-wide spectrum of tandem repeat expansions in 338,963 humans
• Ya Cui,
• Wenbin Ye,
• Jason Sheng Li,
• Jingyi Jessica Li,
• Eric Vilain,
• Tamer Sallam,
• Wei Li
Open Access
The Tandem Repeat Genome Aggregation Database (TR-gnomAD) is a biobank-scale reference of 0.86 million TRs derived from 338,963 whole-genome sequencing (WGS) samples of diverse ancestries.