Type 1 Treg cells promote the generation of CD8+ tissue-resident memory T cells

Ferreira, Cristina; Barros, Leandro; Baptista, Mónica; Blankenhaus, Birte; Barros, André; Figueiredo‐Campos, Patrícia; Konjar, Špela; Laine, Anne; Kamenjarin, Nadine; Stojanović, Ana; Cerwenka, Adelheid; Probst, Hans; Marie, Julien C.; Veldhoen, Marc

doi:10.1038/s41590-020-0674-9

Cited by 76 publications

(84 citation statements)

References 65 publications

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“…Tumor immunotherapy has made tremendous progress, changing the treatment pattern of many cancers 8,9 . We found a positive correlation of CCDC80 expression with the infiltration of B cells ( P = 5.32 × 10 −02 ), dendritic cells ( P = 7.04 × 10 −40 ), macrophage cells ( P = 3.52 × 10 −56 ), CD4 + T cells ( P = 8.64 × 10 −29 ), CD8 + T cells ( P = 4.14 × 10 −08 ), and neutrophil cells ( P = 3.34 × 10 −28 ) (Figure 3E).…”

Section: Figurementioning

confidence: 81%

“…Tumor immunotherapy has made tremendous progress, changing the treatment pattern of many cancers. 8,9 We found a positive correlation of CCDC80 expression with the infiltration of B cells (P = 5.32 × 10 −02 ), dendritic cells (P = 7.04 × 10 −40 ), macrophage cells (P = 3.52 × 10 −56 ), CD4 + T cells (P = 8.64 × 10 −29 ), CD8 + T cells (P = 4.14 × 10 −08 ), and neutrophil cells (P = 3.34 × 10 −28 ) ( Figure 3E). Furthermore, we validated the results by using patient samples and found that B cells, CD4 + T cells, CD8 + T cells, and neutrophil cells had a positive correlation with CCDC80 expression ( Figure 3F and G).…”

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confidence: 99%

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A prognostic stemness biomarker CCDC80 reveals acquired drug resistance and immune infiltration in colorectal cancer

Wang

Bai

et al. 2020

Clinical & Translational Med

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To the Editor, Colorectal cancer (CRC) is a malignance ranking the third cause of death in malignant tumors. 1 The high mortality of CRC is mainly caused by frequent postoperative metastasis and multidrug resistance. 2 A group of cancer stem cells (CSCs) have been discovered in CRC and the mRNA expression-based stemness index (mRNAsi) was considered as a novel indicator to measure cancer development and drug resistance. 3,4 In the present study, we first explored the prognosis of mRNAsi in CRC patients and identified the critical genes related to immune infiltration and drug resistance. The mRNAsi was much lower in normal samples than that in CRC tissues (P value = 7.458 × 10 −18) and indicated a favorable prognosis in patients with CRC (P = .016), which was inconsistent with our general understanding in other type of cancers (Figure 1A and B). 5-7 In addition, the mRNAsi had no relationship with clinical characteristics, including age, gender, tumor, node, metastasis (TNM) stage, and grade (Figure S1A). To explore the unique characteristic of mRNAsi in CRC, we performed the weighted gene co-expression network analysis of 6501 differentially expressed genes and identified 17 modules (Figure 1C and Figure S1B and C). Among them, the brown, green, and yellow modules showed significant relationship with mRNAsi with correlation index −0.71 (P = 4 × 10 −55), −0.71 (P = 8 × 10 −57), and 0.71 (P = 1 × 10 −55), respectively (Figure 1D). In total, 193 critical genes related to mRNAsi (135 genes in brown, 48 genes in green, and 10 genes in yellow) were filtrated (Figure 1E, Table S1). We found 24 key genes were significant closely associated with poor prognosis in CRC by univariate analysis (Figure 1F, Table S2). Causal relationship with proteins were analyzed by DisNor and indicated that these genes were closely connected and associated with adipogenesis (Figure 1G). This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Section: Figurementioning

confidence: 81%

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confidence: 99%

A prognostic stemness biomarker CCDC80 reveals acquired drug resistance and immune infiltration in colorectal cancer

Wang

Bai

et al. 2020

Clinical & Translational Med

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“…Additionally, CXCR3-directed localization of type I Treg expressing the TGF-β activating integrin, αvβ8, within local inflammatory sites promotes CD8 + T RM generation in the intestine, liver, and lung. Positioning of these Treg adjacent to effector CD8 + T cells promotes CD8 + T RM generation via activated TGF-β availability ( 115 ). In contrast, generation of CD8 + CD103 − T RM following oral Yptb infection is independent of TGF-β signaling, but requires CXCR3-dependent clustering of effector CD8 + T cells with CXCL10-producing CX3CR1 + intestinal cells in areas of inflammation within the intestinal lamina propria, suggesting that the microenvironment formed by immune cell aggregates supports CD8 + T RM formation ( 116 ).…”

Section: Stage 2: Mechanisms That Encourage Cd8 + T Rm To Settle In Peripheral Tissuesmentioning

confidence: 99%

Discipline in Stages: Regulating CD8+ Resident Memory T Cells

Mora-Buch

Bromley

2021

Front. Immunol.

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Resident memory CD8+ T (TRM) cells are a lymphocyte lineage distinct from circulating memory CD8+ T cells. TRM lodge within peripheral tissues and secondary lymphoid organs where they provide rapid, local protection from pathogens and control tumor growth. However, dysregulation of CD8+ TRM formation and/or activation may contribute to the pathogenesis of autoimmune diseases. Intrinsic mechanisms, including transcriptional networks and inhibitory checkpoint receptors control TRM differentiation and response. Additionally, extrinsic stimuli such as cytokines, cognate antigen, fatty acids, and damage signals regulate TRM formation, maintenance, and expansion. In this review, we will summarize knowledge of CD8+ TRM generation and highlight mechanisms that regulate the persistence and responses of heterogeneous TRM populations in different tissues and distinct microenvironments.

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“…It is surprising that pulmonary monocytes and type 1 regulatory T (T reg ) cells also contribute to the differentiation. Pulmonary monocytes are the major cells to present pathogen antigens, while type 1 T reg cells promote the bioavailability of TGF-β ( 41 , 42 ). As mentioned above, CD4+ T RM cells have different development pathways compared with CD8+ T RM cells.…”

Section: Development Of Lung T Rm Cellsmentioning

confidence: 99%

Legend of the Sentinels: Development of Lung Resident Memory T Cells and Their Roles in Diseases

Qian

Zhu

et al. 2021

Front. Immunol.

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SARS-CoV-2 is wreaking havoc around the world. To get the world back on track, hundreds of vaccines are under development. A deeper understanding of how the immune system responds to SARS-CoV-2 re-infection will certainly help. Studies have highlighted various aspects of T cell response in resolving acute infection and preventing re-infections. Lung resident memory T (TRM) cells are sentinels in the secondary immune response. They are mostly differentiated from effector T cells, construct specific niches and stay permanently in lung tissues. If the infection recurs, locally activated lung TRM cells can elicit rapid immune response against invading pathogens. In addition, they can significantly limit tumor growth or lead to pathologic immune responses. Vaccines targeting TRM cells are under development, with the hope to induce stable and highly reactive lung TRM cells through mucosal administration or “prime-and-pull” strategy. In this review, we will summarize recent advances in lung TRM cell generation and maintenance, explore their roles in different diseases and discuss how these cells may guide the development of future vaccines targeting infectious disease, cancer, and pathologic immune response.

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Type 1 Treg cells promote the generation of CD8+ tissue-resident memory T cells

Cited by 76 publications

References 65 publications

A prognostic stemness biomarker CCDC80 reveals acquired drug resistance and immune infiltration in colorectal cancer

A prognostic stemness biomarker CCDC80 reveals acquired drug resistance and immune infiltration in colorectal cancer

Discipline in Stages: Regulating CD8+ Resident Memory T Cells

Legend of the Sentinels: Development of Lung Resident Memory T Cells and Their Roles in Diseases

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