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Tumor Infiltrating Myeloid Cells Confer de novo Resistance to PD-L1 Blockade through EMT-stromal and Tgf-beta Dependent Mechanisms.

Overview of attention for article published in Molecular Cancer Therapeutics, September 2022
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (75th percentile)
  • High Attention Score compared to outputs of the same age and source (85th percentile)

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Title
Tumor Infiltrating Myeloid Cells Confer de novo Resistance to PD-L1 Blockade through EMT-stromal and Tgf-beta Dependent Mechanisms.
Published in
Molecular Cancer Therapeutics, September 2022
DOI 10.1158/1535-7163.mct-22-0130
Pubmed ID
Authors

Haocheng Yu, John P. Sfakianos, Li Wang, Yang Hu, Jorge Daza, Matthew D. Galsky, Harkirat S. Sandhu, Olivier Elemento, Bishoy M. Faltas, Adam M. Farkas, Nina Bhardwaj, Jun Zhu, David J. Mulholland

Abstract

Most bladder cancers are poorly responsive to immune checkpoint blockade (ICB). With the need to define mechanisms of de novo resistance, including contributions from the tumor microenvironment (TME), we used single-cell transcriptional profiling to map tumor infiltrating lymphocytic and myeloid cells in 10 human bladder tumors obtained from patients with a history of smoking either with or without previous ICB. Human data sets were qualitatively compared with single cell data sets from the BBN carcinogen induced mouse model of bladder cancer which was poorly responsive to PD-L1 blockade. We applied an established signature of acquired ICB resistance to these human and murine data sets to reveal conservation in EMT and TGF beta ICB resistance signatures between human-mouse stromal and myeloid cells. Using TCGA transcriptional data sets and deconvolution analysis we showed that patients with a history of smoking and bladder tumors high in M2 macrophage tumor content had a significantly worse survival outcome as compared to nonsmokers that were M2 high. Similarly, BBN induced tumors were high in M2 macrophage content and contained exhausted T-NK cells, thereby modeling the identified TCGA patient subpopulation. The combined targeting of TGF beta + PD-L1 reverted immune cell exclusion and resulted in increased survival and delayed BBN induced tumor progression. Together, these data support a coordinate role for stromal and myeloid cell populations in promoting de novo resistance to PD-L1 blockade particularly in patients with a history of smoking.

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Attention Score in Context

This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 September 2022.
All research outputs
#4,527,269
of 22,137,934 outputs
Outputs from Molecular Cancer Therapeutics
#856
of 3,810 outputs
Outputs of similar age
#47,564
of 193,181 outputs
Outputs of similar age from Molecular Cancer Therapeutics
#2
of 7 outputs
Altmetric has tracked 22,137,934 research outputs across all sources so far. Compared to these this one has done well and is in the 79th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,810 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.0. This one has done well, scoring higher than 77% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 193,181 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 75% of its contemporaries.
We're also able to compare this research output to 7 others from the same source and published within six weeks on either side of this one. This one has scored higher than 5 of them.