The T cell differentiation landscape is shaped by tumour mutations in lung cancer

Abstract

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Nongenetic Evolution Drives Lung Adenocarcinoma Spatial Heterogeneity and Progression

“…Transcriptional and epigenetic heterogeneity has been reported both among and within patients (15)(16)(17)(18)(19). Moreover, molecular diversity can translate in diverse tumor microenvironments, for example in association with variable tumor mutational burden (20)(21)(22)(23) or presence of specific oncogenic alterations (24).…”

Activated regulatory T-cells, dysfunctional and senescent T-cells dominate the microenvironment of pancreatic cancer

“…These cells have been previously described in the context of aging and viral infections and are associated with proliferative senescence and reduced T-cell signalling, whilst maintaining their cytolytic capabilities (27)(28)(29). More recently, these have been observed in the context of cancer (30,31), however, this is the first report to describe them in pancreatic cancer.…”

“…These cells have been previously described in the context of aging and viral infections and are associated with proliferative senescence and reduced T-cell signalling, whilst maintaining their cytolytic capabilities [27, 28, 29]. More recently, these have been observed in the context of cancer [30, 31], however, this is the first report to describe them in pancreatic cancer. Two suppressive populations with negative immune modulatory effects were identified: (i) a metacluster of FoxP3 + CD8 + “regulatory” T-cells (metacluster 12), which was only present in 2 out of the 8 patients (Fig.…”

Single Cell Analysis of Regions of Interest (SCARI) using a Novel Photoswitchable Tag

“…The activation and differentiation state of immune cells and other cells is critically dependent on their interaction with environmental signals. For example, recent data from Ghorani et al 34 demonstrate that differences in the genetic make-up of distinct areas within individual human tumors coincide with variability in immune infiltrate of these areas. In other words, within human tumors, the local microenvironment is shaped by cellular interactions, either involving direct cell-cell contact or soluble mediators.…”