Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours

Milner, J. Justin; Toma, Clara; Yu, Bingfei; Zhang, Kai; Omilusik, Kyla; Phan, Anthony T.; Wei, Dapeng; Getzler, Adam J.; Nguyen, Toan; Crotty, Shane; Wang, Wei; Pipkin, Matthew E.; Goldrath, Ananda W.

doi:10.1038/nature24993

Cited by 515 publications

(706 citation statements)

References 39 publications

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“…T RM are transcriptionally distinct from circulating memory T cells (Milner et al, 2017; Mackay et al, 2013), suggesting an alternate or less prominent role of FOXO1 for T RM maintenance. As such, T RM in the IEL do not get replenished by circulating memory T cells (Masopust et al, 2010), and they display a lower turnover rate than circulating memory T cells (Masopust et al, 2006), indicating that the per cell longevity (of T RM ) is independent of FOXO1 expression.…”

Section: Discussionmentioning

confidence: 99%

Active Maintenance of T Cell Memory in Acute and Chronic Viral Infection Depends on Continuous Expression of FOXO1

et al. 2018

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SUMMARY Immunity following an acutely resolved infection or the long-term equipoise of chronic viral infections often depends on the maintenance of antigen-specific CD8+ T cells, yet the ongoing transcriptional requirements of these cells remain unclear. We show that active and continuous programming by FOXO1 is required for the functional maintenance of a memory population. Upon Foxo1 deletion following resolution of an infection, memory cells rapidly lost their characteristic gene expression, gradually declined in number, and were impaired in self-renewal. This was extended to chronic infections, as a loss of FOXO1 during a persistent viral infection led to a rapid decline of the TCF7 (a.k.a. TCF1)-expressing memory-like subset of CD8+ T cells. We further establish FOXO1 regulation as a characteristic of human memory CD8+ T cells. Overall, we show that the molecular and functional longevity of a memory T cell population is actively maintained by the transcription factor FOXO1.

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Section: Discussionmentioning

confidence: 99%

Active Maintenance of T Cell Memory in Acute and Chronic Viral Infection Depends on Continuous Expression of FOXO1

et al. 2018

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“…In cancer, T RM cells are reported to delay tumour growth and prolong survival [32]. Additionally, T RM cells are necessary for the efficacy of cancer vaccine [11, 33].…”

Section: Discussionmentioning

confidence: 99%

Tissue-resident memory T cells are epigenetically cytotoxic with signs of exhaustion in human urinary bladder cancer

Hartana

Bergman

Broomé

et al. 2018

Clinical and Experimental Immunology

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SummaryTissue‐resident memory T (TRM) cells are CD8+ T lymphocytes that reside in the tissues, including tumours. This T cell subset possesses a magnitude of cytotoxicity, but its epigenetic regulation has not been studied. Here, we investigate the impact of perforin DNA methylation in TRM cells and correlate it with their functional potential. Fifty‐three urothelial urinary bladder cancer (UBC) patients were recruited prospectively. The DNA methylation status of the perforin gene (PRF1) locus in TRM cells was investigated by pyrosequencing. Flow cytometry with ViSNE analysis and in‐vitro stimulation were used to evaluate TRM cell phenotypes. We discovered that tumour TRM cells have low DNA methylation in the PRF1 locus (32·9% methylation), which corresponds to increased numbers of perforin‐expressing TRM cells. Surprisingly, programmed cell death 1 (PD‐1) expression is high in tumour TRM cells, suggesting exhaustion. Following interleukin‐15 and T cell receptor stimulation, perforin and T‐bet expressions are enhanced, indicating that TRM cells from tumours are not terminally exhausted. Moreover, a high number of TRM cells infiltrating the tumours corresponds to lower tumour stage in patients. In conclusion, TRM cells from UBC tumours are epigenetically cytotoxic with signs of exhaustion. This finding identifies TRM cells as potential new targets for cancer immunotherapy.

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“…Common T RM transcriptional program is active in kidney T RM cells as deficiency in transcription factors Blimp-1, Hobit or Runx3 leads to impaired maintenance of kidney T RM cells. 111,112 Similar to skin, lung and salivary gland T RM cells, the long-term maintenance of kidney T RM cells is IL-15-dependent. 60,94 However, the protective function of kidney T RM cells remains to be demonstrated.…”

Section: Tissue Specific Features Of Trm Cellsmentioning

confidence: 99%

“…In addition, Runx3 is also a driver for both human and mouse CD8 + tumor-infiltrating lymphocytes (TILs) that exhibit characteristics of T RM cells. 112 …”

Section: Transcriptional Regulation Of Trm Cellsmentioning

confidence: 99%

Tissue-Specific Control of Tissue-Resident Memory T Cells

Liu

Zhang

2018

Crit Rev Immunol

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Tissue-resident memory T (TRM) cells have emerged to be a major component of T cell biology. Recent investigations have greatly advanced our understanding of TRMs. Common features have been discovered to distinguish memory T cells residing in various mucosal and non-mucosal tissues from their circulating counterparts. Given that most organs and tissues contain unique microenvironment, local signal-induced tissue-specific features are tightly associated with the differentiation, homeostasis and protective functions of TRMs. We will discuss the recent advances in TRM field with a special emphasis on the interaction between local signals and TRM cells in the context of individual tissue environment.

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Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours

Cited by 515 publications

References 39 publications

Active Maintenance of T Cell Memory in Acute and Chronic Viral Infection Depends on Continuous Expression of FOXO1

Active Maintenance of T Cell Memory in Acute and Chronic Viral Infection Depends on Continuous Expression of FOXO1

Tissue-resident memory T cells are epigenetically cytotoxic with signs of exhaustion in human urinary bladder cancer

Tissue-Specific Control of Tissue-Resident Memory T Cells

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