4.6 Review

Exhausted CD8+T cells face a developmental fork in the road

相关参考文献

注意:仅列出部分参考文献,下载原文获取全部文献信息。
Article Immunology

Bispecific PD1-IL2v and anti-PD-L1 break tumor immunity resistance by enhancing stem-like tumor- reactive CD8+T cells and reprogramming macrophages

Melanie Tichet et al.

Summary: PD1-IL2v is an engineered immunocytokine that delivers IL2v precisely to PD-1+ T cells in the tumor microenvironment, resulting in infiltration by stem-like CD8+ T cells and enhanced tumor regression and survival in mice. Combining PD1-IL2v with anti-PD-L1 improves therapeutic efficacy by reprogramming tumor-associated macrophages and enhancing T cell receptor immune repertoire diversity. These findings support the clinical evaluation of PD1-IL2v and anti-PD-L1 combination therapy in immunotherapy-resistant tumors infiltrated with PD-1+ stem-like T cells.

IMMUNITY (2023)

Review Immunology

Epigenetic regulation of T cell exhaustion

Julia A. Belk et al.

Summary: This review article examines the epigenetic underpinnings of T cell exhaustion during viral infections, cancer, autoimmunity, and T cell therapies. It discusses the technologies used to study the epigenome and highlights emerging multi-omic and genome engineering approaches for investigating T cell exhaustion and potential therapeutic opportunities.

NATURE IMMUNOLOGY (2022)

Article Multidisciplinary Sciences

MYB orchestrates T cell exhaustion and response to checkpoint inhibition

Carlson Tsui et al.

Summary: This study reveals that CD62L(+) T-PEX cells, maintained by the transcription factor MYB, play a crucial role in maintaining the proliferative potential, multipotency, and repopulation capacity of exhausted T cells during chronic infection, thus contributing to long-term antiviral immunity and responsiveness to immunotherapy.

NATURE (2022)

Article Immunology

Clonal lineage tracing reveals mechanisms skewing CD8+ T cell fate decisions in chronic infection

Moujtaba Y. Kasmani et al.

Summary: Using single-cell RNA and TCR sequencing, researchers investigated the developmental relationships and fate decisions of CD8(+) T cells during chronic infection. They found substantial clonal and phenotypic diversity, and identified a subset of intermediate cells that can differentiate into terminal effector and exhausted cells. Type I IFN and IRF7 were found to drive exhaustion, while Zeb2 was critical for effector cell generation. TCR avidity correlated with exhausted fate and SHP-1 selectively restricted accumulation of low-avidity effector cells.

JOURNAL OF EXPERIMENTAL MEDICINE (2022)

Article Multidisciplinary Sciences

PD-1-cis IL-2R agonism yields better effectors from stem-like CD8+ T cells

Laura Codarri Deak et al.

Summary: The study shows that PD1-IL2v can induce the differentiation of stem-like CD8(+) T cells into better effector cells by binding to PD-1, without the need for CD25 binding. PD1-IL2v has superior efficacy compared to PD-1 or PD-L1 blocking antibodies, as it avoids the accumulation of terminally differentiated and exhausted T cells.

NATURE (2022)

Article Multidisciplinary Sciences

PD-1 combination therapy with IL-2 modifies CD8+ T cell exhaustion program

Masao Hashimoto et al.

Summary: The study showed that combination therapy with PD-1 blockade and IL-2 during chronic lymphocytic choriomeningitis virus infection significantly alters the differentiation program of CD8(+) T cells, resulting in the generation of highly functional effector CD8(+) T cells that mediate viral control, thus providing a new perspective for cancer treatment.

NATURE (2022)

Article Immunology

Divergent clonal differentiation trajectories of T cell exhaustion

Bence Daniel et al.

Summary: In this study, the authors generate a single-cell multiomic atlas of T cell exhaustion in chronic viral infection, revealing molecular programs and clonal differentiation trajectories of exhausted T cell subsets. The results show that T cell receptor signal strength is a driver of clonal fate in T cell exhaustion.

NATURE IMMUNOLOGY (2022)

Article Immunology

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

Josephine R. Giles et al.

Summary: This study used longitudinal single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin sequencing analyses to uncover new subsets of CD8(+) T cells and explore the epigenetic differences in T-ex cell subsets in different infection states.

NATURE IMMUNOLOGY (2022)

Article Immunology

Single-cell analyses identify circulating anti-tumor CD8 T cells and markers for their enrichment

Kristen E. Pauken et al.

Summary: Monitoring anti-tumor CD8(+) T cell responses in the blood has great therapeutic potential. By using single-cell RNA and TCR sequencing, researchers detected and characterized tumor-matching CD8(+) T cells in blood samples of mice and melanoma patients. These cells showed increased activation compared to nonmatching T cells and were found to be less exhausted than their counterparts in tumors. The study also revealed that PD-1 had poor sensitivity for identifying tumor-matching cells, and identified candidate cell surface markers for these cells in mice and patients.

JOURNAL OF EXPERIMENTAL MEDICINE (2021)

Article Multidisciplinary Sciences

Pan-cancer single cell landscape of tumor-infiltrating T cells

Liangtao Zheng et al.

Summary: This study constructed a pan-cancer atlas of T cells across 21 cancer types, revealing different composition patterns and state-transition paths of T cells. The correlation between certain T cell populations and patient characteristics sheds light on possible determinants of the tumor microenvironment, providing new insights into T cell immunity and precision immunotherapy.

SCIENCE (2021)

Article Multidisciplinary Sciences

T-cell CX3CR1 expression as a dynamic blood-based biomarker of response to immune checkpoint inhibitors

Takayoshi Yamauchi et al.

Summary: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment but durable response is limited. CX3CR1, a marker of T-cell differentiation, is investigated as a predictor of response to ICI therapy. Treatment with ICI increases the frequency of circulating CX3CR1(+)CD8(+) T cells and correlates with response and survival in patients with non-small cell lung cancer.

NATURE COMMUNICATIONS (2021)

Article Oncology

Harnessing the IL-21-BATF Pathway in the CD8+ T Cell Anti-Tumor Response

Paytsar Topchyan et al.

Summary: Our study investigates the dysfunction of CD8(+) T cells in cancer and how they can be enhanced by CD4(+) T cells or modification to improve their effector function against tumors. We found that BATF may play a key role in regulating the anti-tumor function of CD8(+) T cells, providing insights for novel therapeutic treatments for cancer patients.

CANCERS (2021)

Article Immunology

Identification of a T-bethi Quiescent Exhausted CD8 T Cell Subpopulation That Can Differentiate into TIM3+CX3CR1+ Effectors and Memory-like Cells

Saravanan Raju et al.

Summary: In a mouse model of chronic lymphocytic choriomeningitis virus infection, a subset of CX3CR1(+) CD8 T cells was identified to contain a distinct TIM3-PD-1(lo) subpopulation, different from the proliferative effector subset. These TIM3-CX3CR1(+) cells were quiescent and expressed a low level of the transcription factor TCF-1, resembling TCF-1(hi) progenitor CD8 T cells. This subset appears to support the generation of an effector pool from TCF-1(hi) progenitors and contribute to memory-like cells following viral clearance.

JOURNAL OF IMMUNOLOGY (2021)

Article Immunology

BATF and IRF4 cooperate to counter exhaustion in tumor-infiltrating CAR T cells

Hyungseok Seo et al.

Summary: BATF and IRF4 cooperate to counter T cell exhaustion in mouse tumor models, promoting better tumor control by CAR T cells.

NATURE IMMUNOLOGY (2021)

Article Immunology

BATF regulates progenitor to cytolytic effector CD8+ T cell transition during chronic viral infection

Yao Chen et al.

Summary: During chronic viral infection, distinct subsets of effector CD8(+) T cells can arise, including progenitors, exhausted cells, and cytotoxic effector cells. The differentiation of CX(3)CR1(+) effector cells is regulated by Tbx21 and BATF transcription factors.

NATURE IMMUNOLOGY (2021)

Article Immunology

A reservoir of stem-like CD8+ T cells in the tumor-draining lymph node preserves the ongoing antitumor immune response

Kelli A. Connolly et al.

Summary: Tumor-specific CD8(+) T cells in tumor-draining lymph nodes share similarities with T-SL from chronic infections, serving as developmental precursors for intratumoral TCF1(+) T cells, supporting a critical role in sustaining antitumor T cells during tumor development and protecting them from terminal differentiation in the tumor microenvironment.

SCIENCE IMMUNOLOGY (2021)

Review Immunology

A guide to cancer immunotherapy: from T cell basic science to clinical practice

Alex D. Waldman et al.

NATURE REVIEWS IMMUNOLOGY (2020)

Article Immunology

Precursor exhausted T cells: key to successful immunotherapy?

Axel Kallies et al.

NATURE REVIEWS IMMUNOLOGY (2020)

Article Multidisciplinary Sciences

NR4A transcription factors limit CAR T cell function in solid tumours

Joyce Chen et al.

NATURE (2019)

Article Immunology

CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer

Laura M. McLane et al.

Annual Review of Immunology (2019)

Article Multidisciplinary Sciences

TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion

Omar Khan et al.

NATURE (2019)

Article Multidisciplinary Sciences

Proliferation-competent Tcf1+CD8 T cells in dysfunctional populations are CD4 T cell help independent

Kristiyan Kanev et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

Article Oncology

T Cell Dysfunction in Cancer

Daniela S. Thommen et al.

CANCER CELL (2018)

Article Immunology

High-dimensional single cell analysis identifies stem-like cytotoxic CD8(+) T cells infiltrating human tumors

Jolanda Brummelman et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2018)

Article Biochemistry & Molecular Biology

Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma

Moshe Sade-Feldman et al.

Article Multidisciplinary Sciences

Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy

Se Jin Im et al.

NATURE (2016)

Article Multidisciplinary Sciences

The epigenetic landscape of T cell exhaustion

Debattama R. Sen et al.

SCIENCE (2016)

Article Multidisciplinary Sciences

Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade

Kristen E. Pauken et al.

SCIENCE (2016)

Review Immunology

Overcoming T cell exhaustion in infection and cancer

Kristen E. Pauken et al.

TRENDS IN IMMUNOLOGY (2015)

Article Immunology

T cell differentiation in chronic infection and cancer: functional adaptation or exhaustion?

Daniel E. Speiser et al.

NATURE REVIEWS IMMUNOLOGY (2014)

Article Immunology

T cells maintain an exhausted phenotype after antigen withdrawal and population reexpansion

Daniel T. Utzschneider et al.

NATURE IMMUNOLOGY (2013)

Article Multidisciplinary Sciences

Progenitor and Terminal Subsets of CD8+ T Cells Cooperate to Contain Chronic Viral Infection

Michael A. Paley et al.

SCIENCE (2012)

Review Immunology

T cell exhaustion

E. John Wherry

NATURE IMMUNOLOGY (2011)

Editorial Material Biochemistry & Molecular Biology

Fractalkine/CX3CL1: A Potential New Target for Inflammatory Diseases

Brian A. Jones et al.

MOLECULAR INTERVENTIONS (2010)

Review Biochemistry & Molecular Biology

Redefining Chronic Viral Infection

Herbert W. Virgin et al.

Article Multidisciplinary Sciences

Selective expansion of a subset of exhausted CD8 T cells by αPD-L1 blockade

Shawn D. Blackburn et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2008)

Article Multidisciplinary Sciences

Restoring function in exhausted CD8 T cells during chronic viral infection

DL Barber et al.

NATURE (2006)

Article Immunology

A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo

M Matloubian et al.

NATURE IMMUNOLOGY (2000)