Back

Spatial dynamics of the tumor microenvironment in emerging resistance to targeted therapy in EGFR-mutated NSCLC

Nakamura, S.; Shibahara, D.; Tanaka, K.; Kishikawa, Y.; Hashisako, M.; Nakatomi, K.; Nakagaki, N.; Kohno, M.; Azuma, K.; Ibusuki, R.; Otsubo, K.; Yoneshima, Y.; Iwama, E.; Oda, Y.; Okamoto, I.

2025-02-13 cancer biology
10.1101/2025.02.10.637543 bioRxiv
Show abstract

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) provide therapeutic benefit in EGFR mutation-positive non-small cell lung cancer, but some individuals develop early resistance. We performed spatial transcriptomics analysis of pre- and posttreatment tumor samples from the same patients to explore the underlying mechanisms of such early resistance. The proportion and activation of fibroblasts increased in association with the development of early resistance, whereas a distinct tumor cell cluster showed activation of tumor necrosis factor- signaling via the NF-{kappa}B pathway even before treatment. Also in the early resistance sample, specific tumor cell clusters interacted with immune and stromal cells. Immature tertiary lymphoid structures (TLSs) were enriched in the early resistance sample, whereas mature TLSs were observed in the long-term response sample. These findings implicate tumor heterogeneity and an inflammatory tumor microenvironment in early EGFR-TKI resistance, providing insight into potential therapeutic strategies to improve treatment outcomes.

Matching journals

The top 5 journals account for 50% of the predicted probability mass.

1
Nature Communications
○ 5641 papers in training set
Top 1%
38.5%
Similar papers in this journal
2
Cell Reports
○ 1498 papers in training set
Top 10%
3.9%
Similar papers in this journal
3
Genome Biology
○ 637 papers in training set
Top 4%
3.3%
Similar papers in this journal
4
Science Advances
● 1243 papers in training set
Top 11%
3.2%
5
Nature
○ 645 papers in training set
Top 5%
3.2%
Similar papers in this journal
50% of probability mass above
6
Cancer Discovery
● 66 papers in training set
Top 0.8%
3.2%
Similar papers in this journal
7
Nature Cancer
○ 39 papers in training set
Top 0.6%
3.1%
8
Cancer Research
● 130 papers in training set
Top 1%
2.6%
9
eLife
● 5828 papers in training set
Top 41%
2.6%
10
Nature Cell Biology
○ 118 papers in training set
Top 1%
2.3%
11
Communications Biology
○ 993 papers in training set
Top 10%
2.3%
12
Nature Genetics
○ 286 papers in training set
Top 3%
2.1%
13
Cancer Cell
○ 42 papers in training set
Top 0.6%
2.1%
14
Genome Medicine
○ 183 papers in training set
Top 2%
1.9%
15
Cell
○ 431 papers in training set
Top 7%
1.5%
16
npj Precision Oncology
○ 53 papers in training set
Top 1%
1.5%
17
Molecular Cell
○ 350 papers in training set
Top 4%
1.1%
18
Cell Reports Medicine
○ 153 papers in training set
Top 4%
1.1%
19
iScience
○ 1154 papers in training set
Top 28%
1.1%
20
Cell Genomics
○ 172 papers in training set
Top 4%
1.0%
21
Cell Research
○ 51 papers in training set
Top 1%
0.8%
22
Nature Methods
○ 385 papers in training set
Top 7%
0.8%
23
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 42%
0.8%
24
Nucleic Acids Research
◐ 1281 papers in training set
Top 14%
0.8%
25
Cell Discovery
○ 57 papers in training set
Top 1%
0.6%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.