Cancer cells are embedded in the tumor microenvironment (TME), a complex ecosystem of stromal cells. Here, we present a 52,698-cell catalog of the TME transcriptome in human lung tumors at single-cell resolution, validated in independent samples where 40,250 additional cells were sequenced. By comparing with matching non-malignant lung samples, we reveal a highly complex TME that profoundly molds stromal cells. We identify 52 stromal cell subtypes, including novel subpopulations in cell types hitherto considered to be homogeneous, as well as transcription factors underlying their heterogeneity. For instance, we discover fibroblasts expressing different collagen sets, endothelial cells downregulating immune cell homing and genes coregulated with established immune checkpoint transcripts and correlating with T-cell activity. By assessing marker genes for these cell subtypes in bulk RNA-sequencing data from 1,572 patients, we illustrate how these correlate with survival, while immunohistochemistry for selected markers validates them as separate cellular entities in an independent series of lung tumors. Hence, in providing a comprehensive catalog of stromal cells types and by characterizing their phenotype and co-optive behavior, this resource provides deeper insights into lung cancer biology that will be helpful in advancing lung cancer diagnosis and therapy.
In the original article, the surname of co-author Wouter Everaerts was spelled incorrectly as "Everaert." It appears correctly in this Correction, and the error has been corrected online.
Highlights d We single-cell RNA-sequenced 56,771 endothelial cells (ECs) from human, mouse, and cultured lung tumor models d Tip ECs were resolved into migratory and basementmembrane remodeling phenotypes d Capillary and venous ECs expressed immunoregulatory gene signatures d Integrated analysis identified collagen modification as an angiogenic pathway
Data from the ESTS database confirmed that lobectomy performed through VATS is associated with a lower incidence of complications compared with thoracotomy.
This study indicates a correlation between complications and early recurrence and its timing. Modified Clavien classification, beside R1-status and EC LNI, appears to be a useful prognostic indicator of early recurrence and its timing. Achieving esophagectomy without postoperative complications is of utmost importance also for oncologic reasons given its negative potential on early oncologic outcome.
Lung transplantation is still limited by the shortage of suitable donor organs. This results in long waiting times for listed patients with a substantial risk (10-15%) of dying before transplantation. All efforts to increase donor awareness through legislation, public campaigns, and training of transplant coordinators and medical ICU staff should be encouraged. Only a minority of cadaveric donors meets the preset ideal lung donor criteria, leaving many transplantable lungs untouched. Donor lung utilization can be further improved by careful selection of extended criteria donors, by active participation of transplant teams in donor management, and by verifying as often as possible the quality of lungs in the donor hospital by a member of the transplant team. This article aims to update the current evidence from the literature to identify and select potential lung donors and to manage cadaveric donors to maximally increase the organ yield for lung transplantation.
The present Consensus Statement represents a collective agreement among 50 international experts to establish a standardized practice of VATS lobectomy for the thoracic surgical community after 20 years of clinical experience.
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