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Proteotoxic stress response drives T cell exhaustion and immune evasion

A proteotoxic stress response specific to exhausted T cells, governed by AKT signaling and accompanied by increased protein translation, represents a mechanistic vulnerability and a new therapeutic target to improve cancer immunotherapies.

Yi Wang
Anjun Ma
Zihai Li
ResearchOpen Access01 Oct 2025
Nature

Volume: 647, P: 1025-1035
Rebalancing TGFβ1/BMP signals in exhausted T cells unlocks responsiveness to immune checkpoint blockade therapy

Cancer immunotherapies can be limited by terminally dysfunctional T cells in the tumor microenvironment. Here the authors present a model of stable human T cell dysfunction to show that TGFβ contributes to this terminal dysfunction which can be therapeutically inhibited by simultaneously blocking TGFβ1 and boosting bone morphogenetic protein (BMP) signaling.

Abbey A. Saadey
Amir Yousif
Hazem E. Ghoneim
Research21 Dec 2022
Nature Immunology

Volume: 24, P: 280-294
T cell exhaustion—a memory locked behind scars

Following clearance of chronic infections, virus-specific CD8⁺ T cells recover a subset of memory-related transcriptome features. Yet their unique open chromatin landscape largely reflects an exhausted or dysfunctional state, limiting their protective memory potential.

Amir Yousif
Hazem E. Ghoneim
News & Views26 Jul 2021
Nature Immunology

Volume: 22, P: 938-940
Enriched grain minerals in Aegilops tauschii-derived common wheat population under heat-stress environments

Amir Ibrahim Ismail Emam
Nasrein Mohamed Kamal
Takayoshi Ishii
ResearchOpen Access15 Feb 2025
Scientific Reports

Volume: 15, P: 1-17
Predicting opioid consumption after surgical discharge: a multinational derivation and validation study using a foundation model

Chris Varghese
Luke Peters
Caroline Reinke
ResearchOpen Access26 Aug 2025
npj Digital Medicine

Volume: 8, P: 1-16
A multinational cross-sectional study on the prevalence and predictors of long COVID across 33 countries

Mohamed Sayed Zaazouee
Eman Ayman Nada
Mohamed Onyango
ResearchOpen Access03 Aug 2025
Scientific Reports

Volume: 15, P: 1-13
Perinatal and neonatal risk factors for retinopathy of prematurity in very low birthweight, very preterm twins: a population-based study

Rachel Shemesh
Tzipi Strauss
Lev Bakhrakh
Research04 Nov 2023
Eye

Volume: 38, P: 902-909

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Proteotoxic stress response drives T cell exhaustion and immune evasion

Rebalancing TGFβ1/BMP signals in exhausted T cells unlocks responsiveness to immune checkpoint blockade therapy

T cell exhaustion—a memory locked behind scars

Enriched grain minerals in Aegilops tauschii-derived common wheat population under heat-stress environments

Predicting opioid consumption after surgical discharge: a multinational derivation and validation study using a foundation model

A multinational cross-sectional study on the prevalence and predictors of long COVID across 33 countries

Perinatal and neonatal risk factors for retinopathy of prematurity in very low birthweight, very preterm twins: a population-based study

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