Immune-molecular interactions in high-grade serous ovarian cancer distinguish long-term survivors DOI Creative Commons
Jeanette E. Boudreau

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(24)

Published: Dec. 15, 2024

The approach and efficacy of treatments for high-grade serous carcinoma (HGSC) the ovary have changed little in decades. Although numerous studies demonstrated immune infiltration as frequent prognostically beneficial, clinical trials immunotherapies generated benefit fewer than 15% patients. In this issue JCI, Nelson colleagues compiled 1,233 HGSC samples from patients across four continents compared molecular immunologic features that associate with long-term survival (greater 10 years). Diversity among tumors is well defined, but study explored combined influence features. Long-term survivors harbored high epithelial content overrepresentation C4/differentiated signature, cytotoxic T B cells infiltrating to tumor epithelium stroma, respectively. These findings highlight might underly poor responsiveness existing most considerations design future, more precise HGSC.

Language: Английский

T cell exhaustion and senescence for ovarian cancer immunotherapy DOI
Jiao Zhao,

Zhongmiao Wang,

Yingying Tian

et al.

Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: 104-105, P. 1 - 15

Published: July 18, 2024

Language: Английский

Citations

11
Crosstalk of T cells within the ovarian cancer microenvironment DOI Creative Commons

Bovannak Stewen Chap,

Nicolas Rayroux,

Alizée J. Grimm

et al.

Trends in cancer, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

3
Integrative spatial omics reveals distinct tumor-promoting multicellular niches and immunosuppressive mechanisms in African American and European American patients with TNBC DOI Open Access
Qian Zhu, Akhila Balasubramanian, Jaya Ruth Asirvatham

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 19, 2024

Abstract Racial disparities in triple-negative breast cancer (TNBC) outcomes have been reported. However, the biological mechanisms underlying these remain unclear. We integrated imaging mass cytometry and spatial transcriptomics, to characterize tumor microenvironment (TME) of African American (AA) European (EA) patients with TNBC. The TME AA was characterized by interactions between endothelial cells, macrophages, mesenchymal-like which were associated poor patient survival. In contrast, EA TNBC-associated niche is enriched T-cells neutrophils suggestive an exhaustion suppression otherwise active T cell responses. Ligand-receptor pathway analyses race-associated niches found TNBC be “immune cold” hence immunotherapy resistant tumors, as ‘inflamed’ tumors that evolved a distinctive immunosuppressive mechanism. Our study revealed presence racially distinct tumor-promoting microenvironments TNBC, may explain clinical outcomes. Statement Significance uncovered contribute observed findings lay groundwork for developing race-specific therapeutic interventions, potentially improving Given chemotherapy anti-PD1 therapy are currently available treatments our finding multicellular niche-associated cell-cell suggest response profiles among patients. Hence, novel insights on molecular cellular stratified race has potential inform personalized treatment strategies.

Language: Английский

Citations

0
Integrated multiomics analysis unveils how macrophages drive immune suppression in breast tumors and affect clinical outcomes DOI Creative Commons
Youness Azimzade, Mads H. Haugen, Vessela N. Kristensen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

Despite thorough characterizations of cellular compositions within the breast tumor microenvironment (TME), their implications for disease progression and patient prognosis are still poorly understood. Unraveling these effects is vital identifying potential targets to improve treatment outcomes. In this study, we devised an explainable machine learning (XML) pipeline scrutinize associations between TME constituents relapse-free survival (RFS). By applying our estimated cell fractions in METABRIC TCGA datasets comparing results with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC), created a comprehensive catalog TME’s role based on 5000 samples. Our findings reveal unexpected dichotomy which macrophages correlate positively pCR but negatively RFS, particularly estrogen receptor-positive (ER+) Luminal A B (LumA/B) cancer subtypes. We show that pattern driven by heterogeneity tumors characterized increasing levels macrophage infiltration. Through imaging mass cytometry (IMC) analysis, discovered tend accumulate vicinity HLA-ABC hi epithelial cells as frequency increases tissues also express elevated protein. Combining IMC single-cell RNA sequencing (scRNA-seq) data, uncovered significant association regulatory exhausted T (T Reg Ex ), suggesting involvement immune suppression, likely creating chronically activated immunosuppressive TME. Subsequent cell-cell communication analysis predicted interactions via ligands SIGLEC9, ALCAM, CSF1, through APP, ANGPTL4, SIGLEC9 signaling. Considering clinical relevance ER+ subtypes, research enhances characterization macrophage-driven suppression identifies immunomodulatory strategies.

Language: Английский

Citations

0
Immune-molecular interactions in high-grade serous ovarian cancer distinguish long-term survivors DOI Creative Commons
Jeanette E. Boudreau

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(24)

Published: Dec. 15, 2024

The approach and efficacy of treatments for high-grade serous carcinoma (HGSC) the ovary have changed little in decades. Although numerous studies demonstrated immune infiltration as frequent prognostically beneficial, clinical trials immunotherapies generated benefit fewer than 15% patients. In this issue JCI, Nelson colleagues compiled 1,233 HGSC samples from patients across four continents compared molecular immunologic features that associate with long-term survival (greater 10 years). Diversity among tumors is well defined, but study explored combined influence features. Long-term survivors harbored high epithelial content overrepresentation C4/differentiated signature, cytotoxic T B cells infiltrating to tumor epithelium stroma, respectively. These findings highlight might underly poor responsiveness existing most considerations design future, more precise HGSC.

Language: Английский

Citations

0