Multimodal profiling of pancreatic cancer reveals a TIMP-1-dominated secretory profile determining pro-tumor immunoinstruction in human cancers.
1/5 보강
The immunosuppressive tumor microenvironment (TME) fosters cancer progression, yet overarching determinants of cancer-borne immunoinstruction remain ill-defined.
APA
Frädrich J, Reyes CM, et al. (2026). Multimodal profiling of pancreatic cancer reveals a TIMP-1-dominated secretory profile determining pro-tumor immunoinstruction in human cancers.. Cell reports. Medicine, 7(1), 102546. https://doi.org/10.1016/j.xcrm.2025.102546
MLA
Frädrich J, et al.. "Multimodal profiling of pancreatic cancer reveals a TIMP-1-dominated secretory profile determining pro-tumor immunoinstruction in human cancers.." Cell reports. Medicine, vol. 7, no. 1, 2026, pp. 102546.
PMID
41564862 ↗
Abstract 한글 요약
The immunosuppressive tumor microenvironment (TME) fosters cancer progression, yet overarching determinants of cancer-borne immunoinstruction remain ill-defined. By multimodal integration of single-nucleus and bulk transcriptomics, proteomics, functional approaches, and clinical parameters, we discover a cancer-immunoinstructive secretory signature (CISS) across multiple human cancers-a set of inflammatory proteins correlated with poor prognosis and pro-tumorigenic TMEs. In pancreatic cancer (PC), CISS arises in pre-malignant epithelium, intensifies along transformation toward most malignant basal-like PC, and particularly correlates with suppressed natural killer (NK) cell activity. The CISS is quantitatively dominated by tissue inhibitor of metalloproteinases (TIMP)-1, most prevalent in TIMP-1/CISS basal-like PC, and causal for PC-cell-mediated NK cell suppression, reflected by impaired cytotoxicity, interleukin-2 (IL-2) responses, and mammalian target of rapamycin (mTOR) signaling. In pre-clinical PC, TIMP-1/CISS proves targetable through combined inhibition of upstream kinases with clinically approved drugs trametinib and nintedanib. Collectively, CISS represents a ubiquitous signature of pro-tumor immunoinstruction with actionable diagnostic and therapeutic potential across human cancers.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
- A Phase I Study of Hydroxychloroquine and Suba-Itraconazole in Men with Biochemical Relapse of Prostate Cancer (HITMAN-PC): Dose Escalation Results.
- Self-management of male urinary symptoms: qualitative findings from a primary care trial.
- Clinical and Liquid Biomarkers of 20-Year Prostate Cancer Risk in Men Aged 45 to 70 Years.
- Diagnostic accuracy of Ga-PSMA PET/CT versus multiparametric MRI for preoperative pelvic invasion in the patients with prostate cancer.
- Comprehensive analysis of androgen receptor splice variant target gene expression in prostate cancer.
- Clinical Presentation and Outcomes of Patients Undergoing Surgery for Thyroid Cancer.