Yap suppresses T-cell function and infiltration in the tumor microenvironment

Stampouloglou, Eleni; Cheng, Nan; Federico, Anthony; Slaby, Emily M.; Monti, Stefano; Szeto, Gregory L.; Varelas, Xaralabos

doi:10.1371/journal.pbio.3000591

Cited by 62 publications

(67 citation statements)

References 89 publications

(107 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activates CTGF and Smad2/3/4 [110] T-cell differentiation Prevents differentiation of T cells toward Treg cells and encourages TH17 helper T-cell differentiation Inhibits differentiation of CD4 + T cells to TH1, TH17, TH2, and Treg fates and reduce tumor infiltration [136,137] Myoblasts and mouse skeletal muscle tissues Promotes myoblast proliferation, muscle growth, and myogenic differentiation, but not regeneration Promotes myoblast proliferation and muscle regeneration, but not differentiation [135] Promoting apoptosis in cancer Represses MYC and its targets in multiple myeloma Binds to p73 and upregulates BAX in various cancer tissues [142,164,165,185,197,198] Ferroptosis in cancer Pro-ferroptotic via regulation of EMP1 in renal cell carcinoma or ANGPTL4 in ovarian cancer Pro-ferroptotic via ACSL4 in colon cancer [131,186,187] apoptosis as well as whether other TFs can switch YAP to a pro-apoptotic transcriptional program.…”

Section: Yesmentioning

confidence: 99%

Context-dependent roles of YAP/TAZ in stem cell fates and cancer

LeBlanc

Ramirez

Kim

2021

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Hippo effectors YAP and TAZ control cell fate and survival through various mechanisms, including transcriptional regulation of key genes. However, much of this research has been marked by conflicting results, as well as controversy over whether YAP and TAZ are redundant. A substantial portion of the discordance stems from their contradictory roles in stem cell self-renewal vs. differentiation and cancer cell survival vs. apoptosis. In this review, we present an overview of the multiple context-dependent functions of YAP and TAZ in regulating cell fate decisions in stem cells and organoids, as well as their mechanisms of controlling programmed cell death pathways in cancer.

show abstract

Section: Yesmentioning

confidence: 99%

Context-dependent roles of YAP/TAZ in stem cell fates and cancer

LeBlanc

Ramirez

Kim

2021

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

show abstract

“…Advances in the field focused on improving CAR-T cell activity include providing cytokine or chemokine support, preventing immunosuppression, and targeting intrinsic pathways to improve CAR-T cell fitness and persistence [ 36 – 39 ]. Recent efforts to provide artificial and immunologically favorable antigen presentation to CAR T cells also aim to improve CAR T cell fitness and persistence.…”

Section: Discussionmentioning

confidence: 99%

Anti-CD19 CAR T cells potently redirected to kill solid tumor cells

Ambrose¹,

Su²,

Wu³

et al. 2021

PLoS ONE

View full text Add to dashboard Cite

Successful CAR T cell therapy for the treatment of solid tumors requires exemplary CAR T cell expansion, persistence and fitness, and the ability to target tumor antigens safely. Here we address this constellation of critical attributes for successful cellular therapy by using integrated technologies that simplify development and derisk clinical translation. We have developed a CAR-CD19 T cell that secretes a CD19-anti-Her2 bridging protein. This cell therapy strategy exploits the ability of CD19-targeting CAR T cells to interact with CD19 on normal B cells to drive expansion, persistence and fitness. The secreted bridging protein potently binds to Her2-positive tumor cells, mediating CAR-CD19 T cell cytotoxicity in vitro and in vivo. Because of its short half-life, the secreted bridging protein will selectively accumulate at the site of highest antigen expression, ie. at the tumor. Bridging proteins that bind to multiple different tumor antigens have been created. Therefore, antigen-bridging CAR-CD19 T cells incorporate critical attributes for successful solid tumor cell therapy. This platform can be exploited to attack tumor antigens on any cancer.

show abstract

“…Interestingly, NRF2 has been linked to the generation of reactive oxygen species that contributes to inflammation in a variety of diseases (61). The HIPPO has been shown to play a role in T cell receptor signaling and in Th17 differentiation (62,63). Systemic administration of agonistic CD40 antibody has been shown to increase CD8+ T cell responses in the lungs of non-human primates (64).…”

Section: Discussionmentioning

confidence: 99%

Lymphocyte-Specific Biomarkers Associated With Preterm Birth and Bronchopulmonary Dysplasia

et al. 2021

View full text Add to dashboard Cite

Many premature babies who are born with neonatal respiratory distress syndrome (RDS) go on to develop Bronchopulmonary Dysplasia (BPD) and later Post-Prematurity Respiratory Disease (PRD) at one year corrected age, characterized by persistent or recurrent lower respiratory tract symptoms frequently related to inflammation and viral infection. Transcriptomic profiles were generated from sorted peripheral blood CD8+ T cells of preterm and full-term infants enrolled with consent in the NHLBI Prematurity and Respiratory Outcomes Program (PROP) at the University of Rochester and the University at Buffalo. We identified outcome-related gene expression patterns following standard methods to identify markers for oxygen utilization and BPD as outcomes in extremely premature infants. We further identified predictor gene sets for BPD based on transcriptomic data adjusted for gestational age at birth (GAB). RNA-Seq analysis was completed for CD8+ T cells from 145 subjects. Among the subjects with highest risk for BPD (born at <29 weeks gestational age (GA); n=72), 501 genes were associated with oxygen utilization. In the same set of subjects, 571 genes were differentially expressed in subjects with a diagnosis of BPD and 105 genes were different in BPD subjects as defined by physiologic challenge. A set of 92 genes could predict BPD with a moderately high degree of accuracy. We consistently observed dysregulation of TGFB, NRF2, HIPPO, and CD40-associated pathways in BPD. Using gene expression data from both premature and full-term subjects (n=116), we identified a 28 gene set that predicted the PRD status with a moderately high level of accuracy, which also were involved in TGFB signaling. Transcriptomic data from sort-purified peripheral blood CD8+ T cells from 145 preterm and full-term infants identified sets of molecular markers of inflammation associated with independent development of BPD in extremely premature infants at high risk for the disease and of PRD among the preterm and full-term subjects.

show abstract

Yap suppresses T-cell function and infiltration in the tumor microenvironment

Cited by 62 publications

References 89 publications

Context-dependent roles of YAP/TAZ in stem cell fates and cancer

Context-dependent roles of YAP/TAZ in stem cell fates and cancer

Anti-CD19 CAR T cells potently redirected to kill solid tumor cells

Lymphocyte-Specific Biomarkers Associated With Preterm Birth and Bronchopulmonary Dysplasia

Contact Info

Product

Resources

About