Tumor-myeloid crosstalk drives therapy resistance in localized bladder cancer
Carvalho, F. L.; Lee, J.; Kalavros, N.; Zhou, Y.; Michaud, D.; Stelter, I.; Siddiqui, H.; Stawiski, K.; Bel, J. P.; Wang, S.; Garza, A.; Bi, K.; Park, J.; Egan, J. M.; Hirohashi, Y.; Epstein, I.; Vlachos, I.; Jia, L.; Kibel, A. S.; Hirsch, M.; Bellmunt, J.; Guerriero, J. L.; Mouw, K. W.; Van Allen, E. M.
Show abstract
Neoadjuvant cisplatin-based chemotherapy results in pathologic complete response for only a minority of patients with muscle-invasive bladder cancer (MIBC), and mechanisms of resistance and the effects of chemotherapy on the MIBC microenvironment remain incompletely understood. Here, we defined the single-cell and spatial transcriptomes of cancer and immune cells from MIBC patients with resistance to cisplatin-based chemotherapy. Tumors with persistent MIBC after chemotherapy harbored cancer cells expressing epithelial-to-mesenchymal programs that were associated with worse overall survival in independent cisplatin-treated bladder cancer cohorts. These cisplatin-resistant tumor cells were infiltrated by macrophages that upregulated tumor permissive programs defined by increased PARP14 expression in spatially resolved multicellular niches. Macrophage reprogramming through PARP14 inhibition sensitized tumors to cisplatin via downregulation of tumor cell pathways implicated in resistance. Our results demonstrate that cancer cells and macrophages cooperate to promote cisplatin resistance and identify macrophage-directed PARP14 inhibition as a novel therapeutic strategy to sensitize MIBC to cisplatin.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Single-Cell RNA Sequencing Reveals the Effects of Chemotherapy on Human Pancreatic Adenocarcinoma and its Tumor Microenvironment 97%
- A single cell atlas reveals distinct immune landscapes in transplant and primary tumors that determine response or resistance to immunotherapy 97%
- Combinatorial immunotherapies overcome MYC-driven immune evasion 97%
Similar papers in this journal
- Cancer-associated fibroblast compositions change with breast cancer progression linking S100A4 and PDPN ratios with clinical outcome 97%
- Differential chromatin accessibility and transcriptional dynamics define breast cancer subtypes and their lineages 96%
- Glutamine mimicry suppresses tumor progression through asparagine metabolism in pancreatic ductal adenocarcinoma 96%
Similar papers in this journal
- Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma 97%
- Generation of a biliary tract cancer cell line atlas reveals molecular subtypes and therapeutic targets 96%
- Single cell view of tumor microenvironment gradients in pleural mesothelioma 96%
Similar papers in this journal
- Genome-wide identification and analysis of prognostic features in human cancers 97%
- Epigenomic signatures as circulating and predictive biomarkers in sarcomatoid renal cell carcinoma 97%
- Identifying a gene signature of metastatic potential by linking pre-metastatic state to ultimate metastatic fate 96%
Similar papers in this journal
- EZH2 synergizes with BRD4-NUT to drive NUT carcinoma growth through silencing of key tumor suppressor genes 97%
- CIP2A interacts with TopBP1 and is selectively essential for DNA damage-induced basal-like breast cancer tumorigenesis 96%
- PAX3-FOXO1 drives targetable cell state-dependent metabolic vulnerabilities in rhabdomyosarcoma 96%
"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.