Re-purposing the pro-senescence properties of doxorubicin to introduce immunotherapy in breast cancer brain metastasis

Uceda-Castro, Rebeca; Margarido, Andreia S.; Cornet, Lesley; Vegna, Serena; Hahn, Kerstin; Song, Ji‐Ying; Putavet, Diana A.; Geldorp, Mariska van; Çitirikkaya, Ceren H.; Keizer, Peter L.J. de; Beek, Leon C. ter; Borst, Gerben R.; Akkari, Leila; Tellingen, Olaf van; Broekman, Marike L. D.; Vennin, Claire; Rheenen, Jacco van

doi:10.1016/j.xcrm.2022.100821

Cited by 15 publications

(17 citation statements)

References 84 publications

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“…Chemotherapeutic drugs that can increase the expression of PD-L1 induce senescence and can sensitize cancer cells to anticancer drugs. Doxorubicin-induced senescence promoted the recruitment of PD-L1-expressing T cells [ 162 ]. Thus, the induction of senescence by chemotherapy may enhance the immunotherapeutic efficacy of anti-PD-L1 antibodies.…”

Section: Discussionmentioning

confidence: 99%

The Potential of Senescence as a Target for Developing Anticancer Therapy

Shim

Jeoung

2023

IJMS

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Senescence occurs in response to various stimuli. Senescence has attracted attention because of its potential use in anticancer therapy as it plays a tumor-suppressive role. It also promotes tumorigeneses and therapeutic resistance. Since senescence can induce therapeutic resistance, targeting senescence may help to overcome therapeutic resistance. This review provides the mechanisms of senescence induction and the roles of the senescence-associated secretory phenotype (SASP) in various life processes, including therapeutic resistance and tumorigenesis. The SASP exerts pro-tumorigenic or antitumorigenic effects in a context-dependent manner. This review also discusses the roles of autophagy, histone deacetylases (HDACs), and microRNAs in senescence. Many reports have suggested that targeting HDACs or miRNAs could induce senescence, which, in turn, could enhance the effects of current anticancer drugs. This review presents the view that senescence induction is a powerful method of inhibiting cancer cell proliferation.

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Section: Discussionmentioning

confidence: 99%

The Potential of Senescence as a Target for Developing Anticancer Therapy

Shim

Jeoung

2023

IJMS

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“…68 Similarly, using various murine models of mammary tumors, doxorubicin was found to prime specific immune response and to trigger the recruitment of PD-1 + T cells at the tumor site. 81 Moreover, doxorubicin improves the efficacy of immunotherapy with anti-PD-1 in such models in a CD8 T cell-dependent manner as observed in colon and lung cancer models.…”

Section: F I G U R E 3 Effects Of Icd Inducers On the Tmementioning

confidence: 96%

Using immunogenic cell death to improve anticancer efficacy of immune checkpoint inhibitors: From basic science to clinical application

Ghiringhelli,

Rébé

2023

Immunological Reviews

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SummaryEven though the discovery of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, a high proportion of patients do not respond. Moreover, some types of cancers are refractory to these treatments. Thus, the need to find predictive biomarkers of efficacy and to evaluate the association with other treatments, such as chemotherapy or radiotherapy, appears to be essential. Because ICIs reactivate or maintain an active status of T cells, one possibility is to combine these treatments with therapies that engage an immune response against tumor cells. Thus, by inducing immunogenic cell death (ICD) of cancer cells, some conventional anticancer treatments induce such immune response and may have an interest to be combined with ICIs. In this review, we explore preclinical studies and clinical trials that evaluate the combination of ICIs with ICD inducers. More than inducing ICD, some of these treatments appear to modulate the tumor microenvironment and more particularly to inhibit immunosuppression, thus improving treatment efficacy.

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“…Another preclinical BCBM mouse model has been used to test the combination of doxorubicin, a chemotherapy drug that induces between other effects senescence, with anti-PD1 to improve the efficacy of immunotherapy. This combination increased the recruitment of T cells to the BM and improved survival in the mice [12].…”

Section: Intracardiac Injectionmentioning

confidence: 98%

Preclinical models to understand the biology and to discover new targets in brain metastases

Kindt

Kotecki

Awada

2023

Current Opinion in Oncology

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Purpose of review Incidence of brain metastases increases overtime therefore it is important to rapidly progress in the discovery of new strategies of treatment for these patients. In consequence, more and more preclinical models of brain metastases (BM) are established to study new treatments for melanoma, lung, and breast cancer BM. Here, we reviewed the most recent findings of new drugs assessed in BM mouse preclinical models. Recent findings BM are a common metastatic site of several types of solid cancers and can be difficult to treat due to the unique environment of the brain and the blood-brain barrier. Currently, several preclinical models of BM have been demonstrated that new molecular targeted therapies, small metabolic inhibitors, immunotherapies or a combination of these drugs with radiotherapy lead to a reduction of BM growth and an improvement of mouse survival. Summary The use of preclinical models of BM is crucial to discover new treatment strategies for patients with BM. In the last years, some new drugs have been highlighted in preclinical models and are now tested in clinical trials including patients with brain metastases.

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Re-purposing the pro-senescence properties of doxorubicin to introduce immunotherapy in breast cancer brain metastasis

Cited by 15 publications

References 84 publications

The Potential of Senescence as a Target for Developing Anticancer Therapy

The Potential of Senescence as a Target for Developing Anticancer Therapy

Using immunogenic cell death to improve anticancer efficacy of immune checkpoint inhibitors: From basic science to clinical application

Preclinical models to understand the biology and to discover new targets in brain metastases

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