Contents | Science Immunology 8, 80

ONLINE COVER Tumor-infiltrating Lymphocytes on JET Patrol. This month’s cover depicts T lymphocytes specific for tumor neoantigens near a cancer cell (yellow) displaying neoantigen peptides on a subset of its cell-surface MHC molecules. JETs (Junctions between Exons and Transposable elements) are a new class of cancer-associated neoantigens made by tumor cells as a result of noncanonical mRNA splicing linking exons to transcripts from transposable elements. Merlotti et al. identified recurrent JETs in human lung tumors and the presence of CD8⁺ T cells specific for JET-encoded epitopes in cancer patients. In a companion paper, Burbage et al. used mouse models to demonstrate that tumor-specific expression of JETs is under epigenetic control.

Credit: Alexis Finkbeiner/Mnemo Therapeutics

Science Immunology

Volume 8|
Issue 80|
Feb 2023

Credit: Alexis Finkbeiner/Mnemo Therapeutics

Research Articles

Dampening type 2 properties of group 2 innate lymphoid cells by a gammaherpesvirus infection reprograms alveolar macrophages

BY
- Pauline Loos
- Jérôme Baiwir
- Céline Maquet
- Justine Javaux
- Rémy Sandor
- François Lallemand
- Thomas Marichal
- Bénédicte Machiels
- Laurent Gillet
24 Feb 2023
NO ACCESS

Gammaherpesvirus infection subverts lung ILC2s thereby promoting alveolar macrophage differentiation with reduced type 2 functions.

Abstract

Immunological dysregulation in asthma is associated with changes in exposure to microorganisms early in life. Gammaherpesviruses (γHVs), such as Epstein-Barr virus, are widespread human viruses that establish lifelong infection and profoundly shape host ...

Noncanonical splicing junctions between exons and transposable elements represent a source of immunogenic recurrent neo-antigens in patients with lung cancer

BY
- Antonela Merlotti
- Benjamin Sadacca
- Yago A. Arribas
- Mercia Ngoma
- Marianne Burbage
- Christel Goudot
- Alexandre Houy
- Ares Rocañín-Arjó
- Ana Lalanne
- Agathe Seguin-Givelet
- Marine Lefevre
- Sandrine Heurtebise-Chrétien
- Blandine Baudon
- Giacomo Oliveira
- Damarys Loew
- Montserrat Carrascal
- Catherine J. Wu
- Olivier Lantz
- Marc-Henri Stern
- Nicolas Girard
- Joshua J. Waterfall
- Sebastian Amigorena
03 Feb 2023
NO ACCESS

Tumor specific transposable elements-exon splicing junctions generate immunogenic HLA-I–bound peptides in NSCLC patients.

Abstract

Although most characterized tumor antigens are encoded by canonical transcripts (such as differentiation or tumor-testis antigens) or mutations (both driver and passenger mutations), recent results have shown that noncanonical transcripts including long ...

Epigenetically controlled tumor antigens derived from splice junctions between exons and transposable elements

BY
- Marianne Burbage
- Ares Rocañín-Arjó
- Blandine Baudon
- Yago A. Arribas
- Antonela Merlotti
- Derek C. Rookhuizen
- Sandrine Heurtebise-Chrétien
- Mengliang Ye
- Alexandre Houy
- Nina Burgdorf
- Guadalupe Suarez
- Marine Gros
- Benjamin Sadacca
- Montserrat Carrascal
- Andrea Garmilla
- Mylène Bohec
- Sylvain Baulande
- Bérangère Lombard
- Damarys Loew
- Joshua J. Waterfall
- Marc-Henri Stern
- Christel Goudot
- Sebastian Amigorena
03 Feb 2023
NO ACCESS

Noncanonical splice junctions between exons and transposable elements are a source of epigenetically-regulated tumor antigens.

Abstract

Oncogenesis often implicates epigenetic alterations, including derepression of transposable elements (TEs) and defects in alternative splicing. Here, we explore the possibility that noncanonical splice junctions between exons and TEs represent a source of ...

Lung epithelial cell–derived C3 protects against pneumonia-induced lung injury

BY
- Sanjaya K. Sahu
- Ayşe N. Ozantürk
- Devesha H. Kulkarni
- Lina Ma
- Ruteja A. Barve
- Linus Dannull
- Angel Lu
- Marick Starick
- Ja’Nia McPhatter
- Lorena Garnica
- Maxwell Sanfillipo-Burchman
- Jeremy Kunen
- Xiaobo Wu
- Andrew E. Gelman
- Steven L. Brody
- John P. Atkinson
- Hrishikesh S. Kulkarni
03 Feb 2023
NO ACCESS

Lung-derived C3 mitigates bacterial pneumonia suggesting a cytoprotective role at barrier surfaces independent of circulating C3.

Abstract

The complement component C3 is a fundamental plasma protein for host defense, produced largely by the liver. However, recent work has demonstrated the critical importance of tissue-specific C3 expression in cell survival. Here, we analyzed the effects of ...

Human IL-23 is essential for IFN-γ–dependent immunity to mycobacteria

BY
- Quentin Philippot
- Masato Ogishi
- Jonathan Bohlen
- Julia Puchan
- Andrés Augusto Arias
- Tina Nguyen
- Marta Martin-Fernandez
- Clement Conil
- Darawan Rinchai
- Mana Momenilandi
- Seyed Alireza Mahdaviani
- Mohammad Keramatipour
- Jérémie Rosain
- Rui Yang
- Taushif Khan
- Anna-Lena Neehus
- Marie Materna
- Ji Eun Han
- Jessica Peel
- Federico Mele
- Marc Weisshaar
- Sandra Jovic
- Paul Bastard
- Romain Lévy
- Tom Le Voyer
- Peng Zhang
- Majistor Raj Luxman Maglorius Renkilaraj
- Carlos A. Arango-Franco
- Simon Pelham
- Yoann Seeleuthner
- Mathieu Pochon
- Manar Mahmoud Ahmad Ata
- Fatima Al Ali
- Mélanie Migaud
- Camille Soudée
- Tatiana Kochetkov
- Anne Molitor
- Raphael Carapito
- Seiamak Bahram
- Bertrand Boisson
- Claire Fieschi
- Davood Mansouri
- Nico Marr
- Satoshi Okada
- Mohammad Shahrooei
- Nima Parvaneh
- Zahra Chavoshzadeh
- Aurélie Cobat
- Dusan Bogunovic
- Laurent Abel
- Stuart G. Tangye
- Cindy S. Ma
- Vivien Béziat
- Federica Sallusto
- Stéphanie Boisson-Dupuis
- Jacinta Bustamante
- Jean-Laurent Casanova
- Anne Puel
10 Feb 2023
NO ACCESS

IL-23 signaling is required for baseline and IL-23-inducible IFN-γ immunity in both Vδ2⁺ γδT and MAIT cells.

Abstract

Patients with autosomal recessive (AR) IL-12p40 or IL-12Rβ1 deficiency display Mendelian susceptibility to mycobacterial disease (MSMD) due to impaired IFN-γ production and, less commonly, chronic mucocutaneous candidiasis (CMC) due to impaired IL-17A/F ...

Heparan sulfate regulates IL-21 bioavailability and signal strength that control germinal center B cell selection and differentiation

BY
- Zhian Chen
- Yanfang Cui
- Yin Yao
- Bo Liu
- Joseph Yunis
- Xin Gao
- Naiqi Wang
- Pablo F. Cañete
- Zewen Kelvin Tuong
- Hongjian Sun
- Hao Wang
- Siling Yang
- Runli Wang
- Yew Ann Leong
- David Simon Davis
- Jiahuan Qin
- Kaili Liang
- Jun Deng
- Conan K. Wang
- Yen-Hua Huang
- Jonathan A. Roco
- Sam Nettelfield
- Huaming Zhu
- Huajun Xu
- Zhijia Yu
- David Craik
- Zheng Liu
- Hai Qi
- Christopher Parish
- Di Yu
17 Feb 2023
NO ACCESS

Low sulfation of heparan sulfate in B_GC cells supports the desensitization to IL-21 and stringent selection for ASC differentiation.

Abstract

In antibody responses, mutated germinal center B (B_GC) cells are positively selected for reentry or differentiation. As the products from GCs, memory B cells and antibody-secreting cells (ASCs) support high-affinity and long-lasting immunity. Positive ...

IL-21R signal reprogramming cooperates with CD40 and BCR signals to select and differentiate germinal center B cells

BY
- Wei Luo
- Laura Conter
- Rebecca A. Elsner
- Shuchi Smita
- Florian Weisel
- Derrick Callahan
- Shuxian Wu
- Maria Chikina
- Mark Shlomchik
17 Feb 2023
NO ACCESS

Reprogrammed IL-21R signaling in GC B cells, in synergy with CD40 signaling, regulates GC B cell positive selection and differentiation.

Abstract

Both B cell receptor (BCR) and CD40 signaling are rewired in germinal center (GC) B cells (GCBCs) to synergistically induce c-MYC and phosphorylated S6 ribosomal protein (p-S6), markers of positive selection. How interleukin-21 (IL-21), a key T follicular ...

pDC-like cells are pre-DC2 and require KLF4 to control homeostatic CD4 T cells

BY
- Patrick Fernandes Rodrigues
- Athanasios Kouklas
- Grozdan Cvijetic
- Nicolas Bouladoux
- Mladen Mitrovic
- Jigar V. Desai
- Djalma S. Lima-Junior
- Michail S. Lionakis
- Yasmine Belkaid
- Robert Ivanek
- Roxane Tussiwand
24 Feb 2023
NO ACCESS

pDC-like cells are circulating precursors for cDC2 that control differentiation of homeostatic CD4⁺ T_H17 cells.

Abstract

Plasmacytoid dendritic cells (pDCs) have been shown to play an important role during immune responses, ranging from initial viral control through the production of type I interferons to antigen presentation. However, recent studies uncovered unexpected ...

Immunosuppressive reprogramming of neutrophils by lung mesenchymal cells promotes breast cancer metastasis

BY
- Zheng Gong
- Qing Li
- Jiayuan Shi
- Peishan Li
- Li Hua
- Leonard D. Shultz
- Guangwen Ren
17 Feb 2023
NO ACCESS

Lung-resident mesenchymal cells reprogram neutrophils to be immunosuppressive cells that facilitate lung metastasis of breast cancer.

Abstract

Neutrophils, the most abundant innate immune cells, function as crucial regulators of the adaptive immune system in diverse pathological conditions, including metastatic cancer. However, it remains largely unknown whether their immunomodulatory functions ...

CD4 binding site immunogens elicit heterologous anti–HIV-1 neutralizing antibodies in transgenic and wild-type animals

BY
- Harry B. Gristick
- Harald Hartweger
- Maximilian Loewe
- Jelle van Schooten
- Victor Ramos
- Thiago Y. Oliveira
- Yoshiaki Nishimura
- Nicholas S. Koranda
- Abigail Wall
- Kai-Hui Yao
- Daniel Poston
- Anna Gazumyan
- Marie Wiatr
- Marcel Horning
- Jennifer R. Keeffe
- Magnus A. G. Hoffmann
- Zhi Yang
- Morgan E. Abernathy
- Kim-Marie A. Dam
- Han Gao
- Priyanthi N. P. Gnanapragasam
- Leesa M. Kakutani
- Ana Jimena Pavlovitch-Bedzyk
- Michael S. Seaman
- Mark Howarth
- Andrew T. McGuire
- Leonidas Stamatatos
- Malcolm A. Martin
- Anthony P. West, Jr.
- Michel C. Nussenzweig
- Pamela J. Bjorkman
10 Feb 2023
NO ACCESS

IOMA germline–targeting Env immunogens induce CD4 binding site–specific broadly neutralizing antibodies against HIV in multiple animal models.

Abstract

Passive transfer of broadly neutralizing anti–HIV-1 antibodies (bNAbs) protects against infection, and therefore, eliciting bNAbs by vaccination is a major goal of HIV-1 vaccine efforts. bNAbs that target the CD4 binding site (CD4bs) on HIV-1 Env are ...

Editor's choice

CD8 T cells are forever

BY
- Jonathan S. Maltzman
03 Feb 2023
NO ACCESS

Iterative acute stimulations can maintain CD8 T cells for longer than their organismal lifespan.

Abstract

Iterative acute stimulations can maintain CD8 T cells for longer than their organismal lifespan.

Editors' Choice

Finding TB vaccine antigens: follow the TCRs

BY
- Andrew Lichtman
03 Feb 2023
Free

TCR sequencing and analysis of predicted CDR3 structures were used to identify TCR similarity groups and the M. Tuberculosis antigens they recognize that associate with infection control or progression.

Abstract

TCR sequencing and analysis of predicted CDR3 structures were used to identify TCR similarity groups and the M. tuberculosis antigens they recognize that associate with infection control or progression.