Journal: Cancer Cell

Abbreviation

Cancer Cell

Publisher

Cell Press

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ISSN

1535-6108
1878-3686

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Publications 1 - 10 of 26
  • The Leukemogenic TCF3-HLF Complex Rewires Enhancers Driving Cellular Identity and Self-Renewal Conferring EP300 Vulnerability
    Item type: Journal Article
    Huang, Yun; Mouttet, Brice; Warnatz, Hans-Jörg; et al. (2019)
    Cancer Cell
  • ARv7 Represses Tumor-Suppressor Genes in Castration-Resistant Prostate Cancer
    Item type: Journal Article
    Cato, Laura; De Tribolet-Hardy, Jonas; Lee, Irene; et al. (2019)
    Cancer Cell
  • Clinical and molecular features of acquired resistance to immunotherapy in non-small cell lung cancer
    Item type: Journal Article
    Memon, Danish; Schoenfeld, Adam J.; Ye, Darwin; et al. (2024)
    Cancer Cell
    Although immunotherapy with PD-(L)1 blockade is routine for lung cancer, little is known about acquired resistance. Among 1,201 patients with non-small cell lung cancer (NSCLC) treated with PD-(L)1 blockade, acquired resistance is common, occurring in >60% of initial responders. Acquired resistance shows differential expression of inflammation and interferon (IFN) signaling. Relapsed tumors can be separated by upregulated or stable expression of IFNγ response genes. Upregulation of IFNγ response genes is associated with putative routes of resistance characterized by signatures of persistent IFN signaling, immune dysfunction, and mutations in antigen presentation genes which can be recapitulated in multiple murine models of acquired resistance to PD-(L)1 blockade after in vitro IFNγ treatment. Acquired resistance to PD-(L)1 blockade in NSCLC is associated with an ongoing, but altered IFN response. The persistently inflamed, rather than excluded or deserted, tumor microenvironment of acquired resistance may inform therapeutic strategies to effectively reprogram and reverse acquired resistance.
  • Coagulation factor X promotes resistance to androgen-deprivation therapy in prostate cancer
    Item type: Journal Article
    Calì, Bianca; Troiani, Martina; Bressan, Silvia; et al. (2024)
    Cancer Cell
    Although hypercoagulability is commonly associated with malignancies, whether coagulation factors directly affect tumor cell proliferation remains unclear. Herein, by performing single-cell RNA sequencing (scRNA-seq) of the prostate tumor microenvironment (TME) of mouse models of castration-resistant prostate cancer (CRPC), we report that immunosuppressive neutrophils (PMN-MDSCs) are a key extra-hepatic source of coagulation factor X (FX). FX activation within the TME enhances androgen-independent tumor growth by activating the protease-activated receptor 2 (PAR2) and the phosphorylation of ERK1/2 in tumor cells. Genetic and pharmacological inhibition of factor Xa (FXa) antagonizes the oncogenic activity of PMN-MDSCs, reduces tumor progression, and synergizes with enzalutamide therapy. Intriguingly, F10high PMN-MDSCs express the surface marker CD84 and CD84 ligation enhances F10 expression. Elevated levels of FX, CD84, and PAR2 in prostate tumors associate with worse survival in CRPC patients. This study provides evidence that FXa directly promotes cancer and highlights additional targets for PMN-MDSCs for cancer therapies.
  • Retinoic acid receptor activation reprograms senescence response and enhances anti-tumor activity of natural killer cells
    Item type: Journal Article
    Colucci, Manuel; Zumerle, Sara; Bressan, Silvia; et al. (2024)
    Cancer Cell
    Cellular senescence can exert dual effects in tumors, either suppressing or promoting tumor progression. The senescence-associated secretory phenotype (SASP), released by senescent cells, plays a crucial role in this dichotomy. Consequently, the clinical challenge lies in developing therapies that safely enhance senescence in cancer, favoring tumor-suppressive SASP factors over tumor-promoting ones. Here, we identify the retinoic-acid-receptor (RAR) agonist adapalene as an effective pro-senescence compound in prostate cancer (PCa). Reactivation of RARs triggers a robust senescence response and a tumor-suppressive SASP. In preclinical mouse models of PCa, the combination of adapalene and docetaxel promotes a tumor-suppressive SASP that enhances natural killer (NK) cell-mediated tumor clearance more effectively than either agent alone. This approach increases the efficacy of the allogenic infusion of human NK cells in mice injected with human PCa cells, suggesting an alternative therapeutic strategy to stimulate the anti-tumor immune response in “immunologically cold” tumors.
  • A lymphotoxin-driven pathway to hepatocellular carcinoma
    Item type: Journal Article
    Haybaeck, Johannes; Zeller, Nicolas; Wolf, Monika Julia; et al. (2009)
    Cancer Cell
  • Inhibition of the Glycolytic Activator PFKFB3 in Endothelium Induces Tumor Vessel Normalization, Impairs Metastasis, and Improves Chemotherapy
    Item type: Journal Article
    Cantelmo, Anna Rita; Conradi, Lena-Christin; Brajic, Aleksandra; et al. (2016)
    Cancer Cell
  • Senescence Reprogramming by TIMP1 Deficiency Promotes Prostate Cancer Metastasis
    Item type: Journal Article
    Guccini, Ilaria; Revandkar, Ajinkya; D'Ambrosio, Mariantonietta; et al. (2021)
    Cancer Cell
    Metastases account for most cancer-related deaths, yet the mechanisms underlying metastatic spread remain poorly understood. Recent evidence demonstrates that senescent cells, while initially restricting tumorigenesis, can induce tumor progression. Here, we identify the metalloproteinase inhibitor TIMP1 as a molecular switch that determines the effects of senescence in prostate cancer. Senescence driven either by PTEN deficiency or chemotherapy limits the progression of prostate cancer in mice. TIMP1 deletion allows senescence to promote metastasis, and elimination of senescent cells with a senolytic BCL-2 inhibitor impairs metastasis. Mechanistically, TIMP1 loss reprograms the senescence-associated secretory phenotype (SASP) of senescent tumor cells through activation of matrix metalloproteinases (MMPs). Loss of PTEN and TIMP1 in prostate cancer is frequent and correlates with resistance to docetaxel and worst clinical outcomes in patients treated in an adjuvant setting. Altogether, these findings provide insights into the dual roles of tumor-associated senescence and can potentially impact the treatment of prostate cancer. © 2020 Elsevier
  • Apolipoprotein E induces pathogenic senescent-like myeloid cells in prostate cancer
    Item type: Journal Article
    Bancaro, Nicolò; Calì, Bianca; Troiani, Martina; et al. (2023)
    Cancer Cell
    Tumor cells promote the recruitment of immunosuppressive neutrophils, a subset of myeloid cells driving immune suppression, tumor proliferation, and treatment resistance. Physiologically, neutrophils are known to have a short half-life. Here, we report the identification of a subset of neutrophils that have upregulated expression of cellular senescence markers and persist in the tumor microenvironment. Senescent-like neutrophils express the triggering receptor expressed on myeloid cells 2 (TREM2) and are more immunosuppressive and tumor-promoting than canonical immunosuppressive neutrophils. Genetic and pharmacological elimination of senescent-like neutrophils decreases tumor progression in different mouse models of prostate cancer. Mechanistically, we have found that apolipoprotein E (APOE) secreted by prostate tumor cells binds TREM2 on neutrophils, promoting their senescence. APOE and TREM2 expression increases in prostate cancers and correlates with poor prognosis. Collectively, these results reveal an alternative mechanism of tumor immune evasion and support the development of immune senolytics targeting senescent-like neutrophils for cancer therapy.
Publications 1 - 10 of 26