Conversations that count: Cellular interactions that drive T cell fate

Duckworth, Brigette C.; Groom, Joanna R

doi:10.1111/imr.12945

Cited by 19 publications

(23 citation statements)

References 209 publications

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“…The well-studied BCL6 (B cell lymphoma-6, also known as ZBTB27) was initially identified as an oncogene frequently translocated/hypermutated in diffuse B cell lymphoma (DLBCL) and follicular lymphoma (FL) cells ( 22 ). In T-cell compartment, BCL6 not only regulates the differentiation of Th cells, but also impacts the generation & maintenance of Tm cells ( Figures 2A, B ) ( 114 , 115 ).…”

Section: Zbtb Proteins Mainly Affecting the Function Of T Cellsmentioning

confidence: 99%

ZBTB Transcription Factors: Key Regulators of the Development, Differentiation and Effector Function of T Cells

Cheng

Gao

et al. 2021

Front. Immunol.

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The development and differentiation of T cells represents a long and highly coordinated, yet flexible at some points, pathway, along which the sequential and dynamic expressions of different transcriptional factors play prominent roles at multiple steps. The large ZBTB family comprises a diverse group of transcriptional factors, and many of them have emerged as critical factors that regulate the lineage commitment, differentiation and effector function of hematopoietic-derived cells as well as a variety of other developmental events. Within the T-cell lineage, several ZBTB proteins, including ZBTB1, ZBTB17, ZBTB7B (THPOK) and BCL6 (ZBTB27), mainly regulate the development and/or differentiation of conventional CD4/CD8 αβ+ T cells, whereas ZBTB16 (PLZF) is essential for the development and function of innate-like unconventional γδ+ T & invariant NKT cells. Given the critical role of T cells in host defenses against infections/tumors and in the pathogenesis of many inflammatory disorders, we herein summarize the roles of fourteen ZBTB family members in the development, differentiation and effector function of both conventional and unconventional T cells as well as the underlying molecular mechanisms.

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Section: Zbtb Proteins Mainly Affecting the Function Of T Cellsmentioning

confidence: 99%

ZBTB Transcription Factors: Key Regulators of the Development, Differentiation and Effector Function of T Cells

Cheng

Gao

et al. 2021

Front. Immunol.

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“…T cells, which differentiate from lymphoid stem cells in the thymus, are important for human defense against disease [ 24 ]. CD8+ cells are an important factor in controlling tumor growth.…”

Section: Resultsmentioning

confidence: 99%

Serum-derived exosomes promote CD8+ T cells to overexpress PD-1, affecting the prognosis of hypopharyngeal carcinoma

Gao

Liu

et al. 2021

Cancer Cell Int

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Background Hypopharyngeal cancer (HPC) is associated with a poor prognosis and a high recurrence rate. Immune escape is one of the reasons for the poor prognosis of malignant tumors. Programmed cell death ligand 1 (PD-L1) and programmed cell death-1 (PD-1) have been shown to play important roles in immune escape. However, the role of PD-1/PD-L1 in HPC remains unclear. In this experiment, we investigated the effect of exosomes from HPC patient serum on CD8+ T cell function and PD-1/PD-L1 expression and, thus, on prognosis. We hope to provide guidance for the identification of new targets for HPC immunotherapy. Methods PD-1 and CD8 expression in 71 HPC tissues and 16 paracarcinoma tissues was detected by immunohistochemistry. Concurrently, the clinicopathological data of the patients were obtained to conduct correlation analysis. Exosomes were isolated from serum and then identified by Western blotting (WB), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Flow cytometry was used to assess the activity of CD8+ T cells after exosome stimulation. The effects of exosomes on the ability of CD8+ T cells to kill FaDu cells were assessed by CCK-8 assay. The expression of IL-10 and TGF-β1 was measured by enzyme-linked immunosorbent assay (ELISA). PD-L1 expression in HPC tissue samples was evaluated by immunohistochemistry, and the relationship between PD-1/PD-L1 expression and prognosis was investigated with patient specimens. Results PD-1 expression was significantly upregulated on CD8+ T cells in tumor tissues compared with those in normal tissues. The overall survival (OS) and disease-free survival (DFS) of PD-1-overexpressing patients were decreased. Serum exosomes from patients can elevate PD-1 expression on CD8+ T cells and suppress their killing capacity and secretory function. The rate of positive PD-L1 expression was increased in HPC tissues compared with paracancerous tissues. The DFS and OS of the PD-1(+)-PD-L1(+) group were significantly lower than those of the PD-1(−)-PD-L1(−) group. Conclusion Our findings indicate that serum exosomes from HPC patients can inhibit CD8+ T cell function and that the PD-1-PD-L1 pathway plays an important role in the immune escape of HPC. Exosomes combined with immunotherapy may guide the treatment of patients with advanced disease in the future.

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“…39 Combined, the use of tissue clearing and LSFM and with reporters to track 3D T cell location established that CD8 + T SLEC and T SCM fates are imprinted in distinct regions and that modulating migration into the lymph node IFR results in increased T SCM differentiation. 16,46…”

Section: Chemokine Receptor Requirements For Cd8 + T Cell Differentia...mentioning

confidence: 99%

Spatial determinates of effector and memory CD8⁺ T cell fates*

Duckworth

Qin

Groom

2021

Immunological Reviews

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The lymph node plays a critical role in mounting an adaptive immune response to infection, clearance of foreign pathogens, and cancer immunosurveillance. Within this complex structure, intranodal migration is vital for CD8 + T cell activation and differentiation. Combining tissue clearing and volumetric light sheet fluorescent microscopy of intact lymph nodes has allowed us to explore the spatial regulation of T cell fates. This has determined that short-lived effector (T SLEC ) are imprinted in peripheral lymph node interfollicular regions, due to CXCR3 migration. In contrast, stem-like memory cell (T SCM ) differentiation is determined in the T cell paracortex. Here, we detail the inflammatory and chemokine regulators of spatially restricted T cell differentiation, with a focus on how to promote T SCM . We propose a default pathway for T SCM differentiation due to CCR7-directed segregation of precursors away from the inflammatory effector niche. Although volumetric imaging has revealed the consequences of intranodal migration, we still lack knowledge of how this is orchestrated within a complex chemokine environment. Toward this goal, we highlight the potential of combining microfluidic chambers with pre-determined complexity and subcellular resolution microscopy.

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Conversations that count: Cellular interactions that drive T cell fate

Cited by 19 publications

References 209 publications

ZBTB Transcription Factors: Key Regulators of the Development, Differentiation and Effector Function of T Cells

ZBTB Transcription Factors: Key Regulators of the Development, Differentiation and Effector Function of T Cells

Serum-derived exosomes promote CD8+ T cells to overexpress PD-1, affecting the prognosis of hypopharyngeal carcinoma

Spatial determinates of effector and memory CD8⁺ T cell fates*

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Conversations that count: Cellular interactions that drive T cell fate

Cited by 19 publications

References 209 publications

ZBTB Transcription Factors: Key Regulators of the Development, Differentiation and Effector Function of T Cells

ZBTB Transcription Factors: Key Regulators of the Development, Differentiation and Effector Function of T Cells

Serum-derived exosomes promote CD8+ T cells to overexpress PD-1, affecting the prognosis of hypopharyngeal carcinoma

Spatial determinates of effector and memory CD8+ T cell fates*

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Spatial determinates of effector and memory CD8⁺ T cell fates*