Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1

Vacchelli, Erika; Ma, Yuting; Baracco, Elisa Elena; Sistigu, Antonella; Enot, David; Pietrocola, Federico; Yang, Heng; Adjemian, Sandy; Chaba, Kariman; Semeraro, Michaela; Signore, Michele; Ninno, Adele De; Lucarini, Valeria; Peschiaroli, Francesca; Businaro, Luca; Gerardino, A.; Manic, Gwenola; Ulas, Thomas; Günther, Patrick; Schultze, Joachim L.; Kepp, Oliver; Stoll, Gautier; Lefèbvre, Céline; Mulot, Claire; Castoldi, Francesca; Rusakiewicz, Sylvie; Ladoire, Sylvain; Apétoh, Lionel; Pedro, José Manuel Bravo-San; Lucattelli, Monica; Delarasse, Cécile; Boige, Valérie; Ducreux, Michel; Delaloge, Suzette; Borg, Christophe; André, Fabrice; Schiavoni, Giovanna; Vitale, Ilio; Laurent‐Puig, Pierre; Mattei, Fabrizio; Zitvogel, Laurence

doi:10.1126/science.aad0779

Cited by 368 publications

(391 citation statements)

References 41 publications

Supporting

Mentioning

386

Contrasting

Order By: Relevance

“…3D). For example, Ccl2 and Clec5a, along with Tnf, are markers of M1-type macrophages, which are known to be tumoricidal (22,23), and Fpr1 is critical to the efficient induction of antitumor immunity in DCs (24). Furthermore, several tumor suppressor genes, such as Grhl1 and Mir133b, are up-regulated by indomethacin-treated supernatants (25).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

PGE2 induced in and released by dying cells functions as an inhibitory DAMP

Hangai

Kimura

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

123

View full text Add to dashboard Cite

Cellular components released into the external milieu as a result of cell death and sensed by the body are generally termed damage-associated molecular patterns (DAMPs). Although DAMPs are conventionally thought to be protective to the host by evoking inflammatory responses important for immunity and wound repair, there is the prevailing notion that dysregulated release of DAMPs can also underlie or exacerbate disease development. However, the critical issue for how resultant DAMP-mediated responses are regulated has heretofore not been fully addressed. In the present study, we identify prostaglandin E2 (PGE2) as a DAMP that negatively regulates immune responses. We show that the production of PGE2 is augmented under cell death-inducing conditions via the transcriptional induction of the cyclooxygenase 2 (COX2) gene and that cell-released PGE2 suppresses the expression of genes associated with inflammation, thereby limiting the cell’s immunostimulatory activities. Consistent with this, inhibition of the PGE2 synthesis pathway potentiates the inflammation induced by dying cells. We also provide in vivo evidence for a protective role of PGE2 released upon acetaminophen-induced liver injury as well as a pathogenic role for PGE2 during tumor cell growth. Our study places this classically known lipid mediator in an unprecedented context—that is, an inhibitory DAMP vis-à-vis activating DAMPs, which may have translational implications for designing more effective therapeutic regimens for inflammation-associated diseases.

show abstract

Section: Resultsmentioning

confidence: 99%

“…3D and refs. 24,25). Although further study is required, such genes would contribute to the suppression of tumor growth.…”

Section: Discussionmentioning

confidence: 99%

PGE2 induced in and released by dying cells functions as an inhibitory DAMP

Hangai

Kimura

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

123

View full text Add to dashboard Cite

show abstract

“…4 Accordingly, there is ample evidence that the long-term fate of breast cancer patients treated with anthracyclines or that of colorectal cancer patients treated with oxaliplatin (OXA) is largely determined by the density of the immune infiltrate (in particular memory effector T cells) at diagnosis, [5][6][7] as well as by dynamic changes in the ratio of cytotoxic T lymphocytes (CTL) versus regulatory T cells occurring shortly after chemotherapy. 8 Loss-of-function alleles of toll-like receptor 4 (TLR4) and formyl peptide receptor 1 (FPR1) also have a negative impact on the therapeutic response of mammary and colorectal carcinoma patients to adjuvant chemotherapies, [9][10][11] further supporting the notion that the immune system dictates (at least part of) the therapeutic response.…”

Section: Introductionmentioning

confidence: 93%

Contribution of RIP3 and MLKL to immunogenic cell death signaling in cancer chemotherapy

Yang¹,

Ma²,

Guo³

et al. 2016

OncoImmunology

Self Cite

146

145

View full text Add to dashboard Cite

Chemotherapy can reinstate anticancer immunosurveillance through inducing tumor immunogenic cell death (ICD). Here, we show that anthracyclines and oxaliplatin can trigger necroptosis in murine cancer cell lines expressing receptor-interacting serine-threonine kinase 3 (RIP3) and mixed lineage kinase domain-like (MLKL). Necroptotic cells featured biochemical hallmarks of ICD and stimulated anticancer immune responses in vivo. Chemotherapy normally killed Rip3 ¡/¡ and Mlkl ¡/¡ tumor cells and normally induced caspase-3 activation in such cells, yet was unable to reduce their growth in vivo. RIP3 or MLKL deficiency abolished the capacity of dying cancer cells to elicit an immune response. This could be attributed to reduced release of ATP and high mobility group box 1 (HMGB1) by RIP3 and MLKL-deficient cells. Measures designed to compensate for deficient ATP and HMGB1 signaling restored the chemotherapeutic response of Rip3 ¡/¡ and Mlkl ¡/¡ cancers. Altogether, these results suggest that RIP3 and MLKL can contribute to ICD signaling and tumor immunogenicity.

show abstract

“…102,103 The current view is that therapeutic agents must induce a sort of "viral mimicry", i.e., a combination of stress signals that are usually linked to viral infection, such as Type-I-IFNs, and are believed to contribute to their clinical effectiveness. We recently showed that Type-I-IFNs lie at the nexus that controls immunogenic cell death (ICD) and constitutes a hallmark of successful chemotherapy.…”

Section: The Role Of Type-i-ifns In Anticancer Therapymentioning

confidence: 99%

Type-I-interferons in infection and cancer: Unanticipated dynamics with therapeutic implications

et al. 2017

Self Cite

View full text Add to dashboard Cite

If there is a great new hope in the treatment of cancer, the immune system is it. Innate and adaptive immunity either promote or attenuate tumorigenesis and so can have opposing effects on the therapeutic outcome. Originally described as potent antivirals, Type-I interferons (IFNs) were quickly recognized as central coordinators of tumor-immune system interactions. Type-I-IFNs are produced by, and act on, both tumor and immune cells being either host-protecting or tumor-promoting. Here, we discuss Type-I-IFNs in infectious and cancer diseases highlighting their dichotomous role and raising the importance to deeply understand the underlying mechanisms so to reshape the way we can exploit Type-I-IFNs therapeutically.

show abstract

Chemotherapy-induced antitumor immunity requires formyl peptide receptor 1

Cited by 368 publications

References 41 publications

PGE2 induced in and released by dying cells functions as an inhibitory DAMP

PGE2 induced in and released by dying cells functions as an inhibitory DAMP

Contribution of RIP3 and MLKL to immunogenic cell death signaling in cancer chemotherapy

Type-I-interferons in infection and cancer: Unanticipated dynamics with therapeutic implications

Contact Info

Product

Resources

About