Similar Datasets
Project description:Gamma delta (γδ) T cells reside within human tissues including tumors, but their role in mediating anti-tumor response with immune checkpoint inhibition is unknown. Using single-cell approaches, we found that kidney cancers are infiltrated by diverse Vδ2- γδ T cells, with equivalent representation of Vδ1+ and Vδ1- cells, that are distinct from γδ T cells found in normal human tissues. These tumor-resident Vδ2- T cells can express the transcriptional program of exhausted alpha beta (ab) CD8+ T cells as well as canonical markers of terminal T cell exhaustion including PD-1, TIGIT and TIM-3. While Vδ2- γδ T cells have blunted IL-2 production, they retain expression of cytolytic effector molecules and costimulatory receptors like 4-1BB. Exhausted Vδ2- γδ T cells are comprised of three distinct populations that lack TCF-7, are clonally expanded, express of cytotoxic molecules, and possess multiple Vδ2- TCRs. Human tumor-derived Vδ2- γδ T cells maintain cytotoxic function and pro-inflammatory cytokine secretion in vitro. The transcriptional program of Vδ2- T cells in pre-treatment tumor biopsies predicted subsequent clinical responses to PD-1 blockade in vivo in cancer patients. Thus, Vδ2- γδ T cells within the tumor microenvironment can contribute to anti-tumor efficacy.
2023-01-31 | GSE223808 | GEO
Project description:Gamma delta (γδ) T cells reside within human tissues including tumors, but their role in mediating anti-tumor response with immune checkpoint inhibition is unknown. Using single-cell approaches, we found that kidney cancers are infiltrated by diverse Vδ2- γδ T cells, with equivalent representation of Vδ1+ and Vδ1- cells, that are distinct from γδ T cells found in normal human tissues. These tumor-resident Vδ2- T cells can express the transcriptional program of exhausted alpha beta (ab) CD8+ T cells as well as canonical markers of terminal T cell exhaustion including PD-1, TIGIT and TIM-3. While Vδ2- γδ T cells have blunted IL-2 production, they retain expression of cytolytic effector molecules and costimulatory receptors like 4-1BB. Exhausted Vδ2- γδ T cells are comprised of three distinct populations that lack TCF-7, are clonally expanded, express of cytotoxic molecules, and possess multiple Vδ2- TCRs. Human tumor-derived Vδ2- γδ T cells maintain cytotoxic function and pro-inflammatory cytokine secretion in vitro. The transcriptional program of Vδ2- T cells in pre-treatment tumor biopsies predicted subsequent clinical responses to PD-1 blockade in vivo in cancer patients. Thus, Vδ2- γδ T cells within the tumor microenvironment can contribute to anti-tumor efficacy.
2023-01-31 | GSE223806 | GEO
Project description:Exhausted intratumoral Vδ2- γδ T cells in human kidney cancer retain effector function
| PRJNA928412 | ENA
Project description:Exhausted intratumoral Vδ2- γδ T cells in human kidney cancer retain effector function [scRNA-seq]
| PRJNA928414 | ENA
Project description:Exhausted intratumoral Vδ2- γδ T cells in human kidney cancer retain effector function [bulk RNA-seq]
| PRJNA928413 | ENA
Project description:The proliferation and interleukin-2 production of CD4(+)CD25(-) αβ T cells were inhibited in a cell-contact manner by Vδ2 γδ T cells. The transcription factor Helios was constitutively expressed in about one-third of circulating γδ T cells and was upregulated by CD28-signaling. Our data suggest that Helios could serve as a marker for differential activation status rather than for regulatory T cells (Treg). Our findings also indicate that the interaction of CD86 on activated Vδ2 T cells and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) on activated αβ T cells mediated the suppression because the suppressive effect was abolished by blocking the CD86:CTLA-4 interaction. Pre-treatment of Vδ2 T cells with Toll-like receptor 2 ligands enhanced phosphorylation of MAPKs, Akt, and NF-κB and partially abrogated the suppressive capacity, whereas on co-cultured responder T cells inhibitory molecules were downregulated and Akt and NF-κB phosphorylation was restored. Our results suggest that the regulation of αβ T cell proliferation by activated Vδ2 T cells might contribute to fine-tuning of αβ T cell responses.
| S-EPMC3997799 | biostudies-literature
Project description:The clinical penetrance of infectious diseases varies considerably among patients with inborn errors of immunity (IEI), even for identical genetic defects. This variability is influenced by pathogen exposure, healthcare access and host-environment interactions. We describe here a patient in his thirties who presented with epidermodysplasia verruciformis (EV) due to infection with a weakly virulent beta-papillomavirus (HPV38) and CD4+ T-cell lymphopenia. The patient was born to consanguineous parents living in the United States. Exome sequencing identified a previously unknown biallelic STK4 stop-gain mutation (p.Trp425X). The patient had no relevant history of infectious disease during childhood other than mild wart-like lesion on the skin, but he developed diffuse large B-cell lymphoma (DLBCL) and EBV viremia with a low viral load in his thirties. Despite his low CD4+ T-cell count, the patient had normal counts of CD3+ cells, predominantly double-negative T cells (67.4%), which turned out to be Vδ2+ γδ T cells. γδ T-cell expansion has frequently been observed in the 33 reported cases with STK4 deficiency. The Vδ2 γδ T cells of this STK4-deficient patient are mostly CD45RA-CD27+CCR7+ central memory γδT cells, and their ability to proliferate in response to T-cell activation was impaired, as was that of CD4+ T cells. In conclusion, γδ T-cell expansion may act as a compensatory mechanism to combat viral infection, providing immune protection in immunocompromised individuals.
| S-EPMC11306306 | biostudies-literature
Project description:Exhausted CD8 T cells during chronic inflammatory responses against viral infections and cancer are phenotypically and functionally heterogeneous. In particular, CD8 T cells with cytolytic effector function have been recently identified among the exhausted CD8 T cell subsets. However, the regulation of their differentiation and function remains largely unknown. Here, we report that Krüppel-like factor 4 (KLF4) is a critical regulator of the exhaustion process, promoting the cytolytic effector function of exhausted CD8 T cells. KLF4-expressing CD8 T cells in exhaustion contexts showed the features of transitory effector CD8 T cells. Enforced KLF4 expression increased CD8 T cell differentiation into transitory effector subsets and enhanced their antitumor immunity. We further demonstrated that KLF4 also showed a capacity of reinvigorating exhausted CD8 T cells. Last, high KLF4 expression was positively correlated with a favorable prognosis in human patients with cancer. Our study highlights the potential impacts of KLF4 on CD8 T cell exhaustion and antitumor immune therapy. Description KLF4 regulates the exhaustion process by promoting CD8 T cell differentiation into cytolytic transitory effector subsets.
| S-EPMC9699681 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-10-24 | GSE212806 | GEO
Project description:Human cytomegalovirus infection in transplant recipients has been associated with adverse renal allograft outcome and with a large γδ T-cell response, but whether both mechanisms are connected is unknown. We previously showed that most expanded circulating cytomegalovirus-responsive γδ T cells express the Fcγ-receptor CD16, suggesting that γδ T cells may participate in allograft lesions mediated by donor-specific antibodies through antibody-dependent cellular cytotoxicity. Here, we show that cytomegalovirus-specific CD16(pos) γδ T cells can perform antibody-dependent cellular cytotoxicity against stromal cells coated with donor-specific antibodies in vitro. In vivo, graft-infiltrating γδ T cells localized in close contact with endothelial cells only in patients who experienced cytomegalovirus infection and were more frequent within peritubular capillaries and glomeruli from antibody-mediated acute rejections than within those from T cell-mediated acute rejections. Finally, a persistently increased percentage of circulating cytomegalovirus-induced γδ T cells correlated inversely with the 1-year eGFR only in kidney recipients with donor-specific antibodies. Collectively, these data support the conclusion that cytomegalovirus-induced γδ T cells are involved in, and may serve as a clinical biomarker of, antibody-mediated lesions of kidney transplants. Moreover, these findings offer a new physiopathologic link between cytomegalovirus infection and allograft dysfunction in recipients with donor-specific antibodies.
| S-EPMC4214528 | biostudies-literature