[HTML][HTML] High-content CRISPR screening

C Bock, P Datlinger, F Chardon, MA Coelho… - Nature Reviews …, 2022 - nature.com
CRISPR screens are a powerful source of biological discovery, enabling the unbiased
interrogation of gene function in a wide range of applications and species. In pooled …

Epigenetic regulation of T cell exhaustion

JA Belk, B Daniel, AT Satpathy - Nature immunology, 2022 - nature.com
Chronic antigen stimulation during viral infections and cancer can lead to T cell exhaustion,
which is characterized by reduced effector function and proliferation, and the expression of …

The primordial differentiation of tumor-specific memory CD8+ T cells as bona fide responders to PD-1/PD-L1 blockade in draining lymph nodes

Q Huang, X Wu, Z Wang, X Chen, L Wang, Y Lu… - Cell, 2022 - cell.com
Summary Blocking PD-1/PD-L1 signaling transforms cancer therapy and is assumed to
unleash exhausted tumor-reactive CD8+ T cells in the tumor microenvironment (TME) …

Shared and distinct biological circuits in effector, memory and exhausted CD8+ T cells revealed by temporal single-cell transcriptomics and epigenetics

JR Giles, SF Ngiow, S Manne, AE Baxter, O Khan… - Nature …, 2022 - nature.com
Naïve CD8+ T cells can differentiate into effector (Teff), memory (Tmem) or exhausted (Tex)
T cells. These developmental pathways are associated with distinct transcriptional and …

Genome-wide CRISPR screens of T cell exhaustion identify chromatin remodeling factors that limit T cell persistence

JA Belk, W Yao, N Ly, KA Freitas, YT Chen, Q Shi… - Cancer cell, 2022 - cell.com
T cell exhaustion limits antitumor immunity, but the molecular determinants of this process
remain poorly understood. Using a chronic stimulation assay, we performed genome-wide …

A genome-scale screen for synthetic drivers of T cell proliferation

M Legut, Z Gajic, M Guarino, Z Daniloski, JA Rahman… - Nature, 2022 - nature.com
The engineering of autologous patient T cells for adoptive cell therapies has revolutionized
the treatment of several types of cancer. However, further improvements are needed to …

RASA2 ablation in T cells boosts antigen sensitivity and long-term function

J Carnevale, E Shifrut, N Kale, WA Nyberg… - Nature, 2022 - nature.com
The efficacy of adoptive T cell therapies for cancer treatment can be limited by suppressive
signals from both extrinsic factors and intrinsic inhibitory checkpoints,. Targeted gene editing …

[HTML][HTML] The mitochondrial pyruvate carrier regulates memory T cell differentiation and antitumor function

M Wenes, A Jaccard, T Wyss, N Maldonado-Pérez… - Cell Metabolism, 2022 - cell.com
Glycolysis, including both lactate fermentation and pyruvate oxidation, orchestrates CD8+ T
cell differentiation. However, how mitochondrial pyruvate metabolism and uptake controlled …

Transcriptional and epigenetic regulators of human CD8+ T cell function identified through orthogonal CRISPR screens

SR McCutcheon, AM Swartz, MC Brown, A Barrera… - Nature Genetics, 2023 - nature.com
Clinical response to adoptive T cell therapies is associated with the transcriptional and
epigenetic state of the cell product. Thus, discovery of regulators of T cell gene networks and …

Stem-like exhausted and memory CD8+ T cells in cancer

T Gebhardt, SL Park, IA Parish - Nature Reviews Cancer, 2023 - nature.com
T cells can acquire a broad spectrum of differentiation states following activation. At the
extreme ends of this continuum are short-lived cells equipped with effector machinery and …