2021
DOI: 10.1038/s41467-021-26091-4
|View full text |Cite
|
Sign up to set email alerts
|

Abstract: Regulatory T (Treg) cells are one of the major immunosuppressive cell types in cancer and a potential target for immunotherapy, but targeting tumor-infiltrating (TI) Treg cells has been challenging. Here, using single-cell RNA sequencing of immune cells from renal clear cell carcinoma (ccRCC) patients, we identify two distinct transcriptional fates for TI Treg cells, Fate-1 and Fate-2. The Fate-1 signature is associated with a poorer prognosis in ccRCC and several other solid cancers. CD177, a cell surface pro… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
2
1

Citation Types

1
19
0

Year Published

2021
2021
2024
2024

Publication Types

Select...
7
1

Relationship

1
7

Authors

Journals

citations
Cited by 41 publications
(20 citation statements)
references
References 45 publications
1
19
0
Order By: Relevance
“…S3D, E). Overall, these data confirm that iCCA-infiltrating Tregs show a heterogeneous pattern and activated phenotype similar to those previously found in other solid tumors [29][30][31][32]. As far as myeloid cells were concerned, tumors were preferentially infiltrated compared to other tissues by CD11b+ CD11c+ HLA-DR high CD1c+ cDC2 (Fig.…”
Section: High-dimensional Flow Cytometry Defines the T Cell And Myelo...supporting
confidence: 89%
See 1 more Smart Citation
“…S3D, E). Overall, these data confirm that iCCA-infiltrating Tregs show a heterogeneous pattern and activated phenotype similar to those previously found in other solid tumors [29][30][31][32]. As far as myeloid cells were concerned, tumors were preferentially infiltrated compared to other tissues by CD11b+ CD11c+ HLA-DR high CD1c+ cDC2 (Fig.…”
Section: High-dimensional Flow Cytometry Defines the T Cell And Myelo...supporting
confidence: 89%
“…scRNA-seq further informed on the characteristics of the different immune cell types and enabled the identification of a major suppressive hub orchestrated by Tregs in the iCCA tumor microenvironment. Compared to the adjacent peritumoral tissues, iCCA-infiltrating Tregs showed features of the hyperactivated effector state previously described in several solid tumors, including melanoma, NSCLC, hepatocellular carcinoma, renal cancer, BC and CRC [29][30][31][32]. Although differences that are yet to be identified might be present according to the specific tumor type, it seems evident that intratumoral Tregs share a core transcriptional and functional program, characterized by the increased expression of inhibitory molecules, chronic immune activation and enhanced suppressive capacity compared to those from the circulation or the peritumoral area.…”
Section: Discussionmentioning
confidence: 60%
“…Tumor-infiltrating Treg cells exhibit certain heterogeneity including two distinct populations, with one population showing strong suppressive capacity. We developed a unique tumor-infiltrating Treg cell signature with the prognostic value superior to some known Treg signatures [ 142 ]. The clinical importance of tumor-infiltrating Treg cells has been correlated with poor prognosis and response to immune perturbation in other studies as well [ 45 , 95 , 143 ].…”
Section: Single-cell Genomics To Study the Tumor Microenvironmentmentioning
confidence: 99%
“…A study observed that anti-PD-1 therapy induces hyper-progression with clonal expansion of tumor-infiltrating Treg cells with upregulation of some genes, including CD177 and BCL2L1 in a leukemic patient [ 144 ], the two genes we found to be elevated specifically in tumor-infiltrating Treg cells. CD177 is a surface protein and may modulate the immune suppressive function and maintain homeostasis of tumor-infiltrating Treg cells in ccRCC [ 142 ]. We have demonstrated that CD177 + tumor-infiltrating Treg cells are hyper-suppressive to effector T cells and anti-CD177 antibody is able to block the suppressive function of CD177 + tumor-infiltrating Treg cells.…”
Section: Single-cell Genomics To Study the Tumor Microenvironmentmentioning
confidence: 99%
“…Indeed, in ccRCC patients, NK cell in ltration in the circulation and tumour was found to be strongly associated with an immunosuppressive phenotype [31]. [32] Regulatory T cells are one of the major immunosuppressive cell types in malignancies and a potential target for immunotherapy [33]. However, our study found that CENPM was positively correlated with these cells, highlighting the immunosuppressive phenotype to some extent.…”
Section: Discussionmentioning
confidence: 54%