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Vacchelli, Erika; Eggermont, Alexander M.M.; Sautès-Fridman, Catheriné; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

doi:10.4161/onci.25238

Cited by 130 publications

(59 citation statements)

References 264 publications

(217 reference statements)

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“…Our results suggest that MDSCs accumulate in tumor-bearing hosts in response to exogenously added TLR2 ligands. Adjuvant immunotherapy for cancer using TLR2 ligands has been proposed and some clinical trials are in progress [36]. Our results, however, unveiled the negative effects of TLR2 ligands on tumor immunity in terms of MDSC frequencies.…”

Section: Discussionmentioning

confidence: 69%

Pam2 lipopeptides systemically increase myeloid-derived suppressor cells through TLR2 signaling

Maruyama

Shime

Takeda

et al. 2015

Biochemical and Biophysical Research Communications

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Section: Discussionmentioning

confidence: 69%

Pam2 lipopeptides systemically increase myeloid-derived suppressor cells through TLR2 signaling

Maruyama

Shime

Takeda

et al. 2015

Biochemical and Biophysical Research Communications

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“…Unfortunately, no in-depth information is available on the mode of action of this agent, an antifungal antibiotic produced by S. fibriatus 49 . However, it is tempting to speculate that septacidin may provoke an ultimately lethal stress response in mammalian cells upon the activation of pattern recognition receptors 50 . This possibility will be actively investigated in our laboratory.…”

Section: Discussionmentioning

confidence: 99%

Screening of novel immunogenic cell death inducers within the NCI Mechanistic Diversity Set

et al. 2014

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Immunogenic cell death (ICD) inducers can be defined as agents that exert cytotoxic effects while stimulating an immune response against dead cell-associated antigens. When initiated by anthracyclines, ICD is accompanied by stereotyped molecular changes, including the pre-apoptotic exposure of calreticulin (CRT) on the cell surface, the lysosomal secretion of ATP during the blebbing phase of apoptosis, and the release of high mobility group box 1 (HMGB1) from dead cells. By means of genetically engineered human osteosarcoma U2OS cells, we screened the 879 anticancer compounds of the National Cancer Institute (NCI) Mechanistic Diversity Set for their ability to promote all these hallmarks of ICD in vitro. In line with previous findings from our group, several cardiac glycosides exhibit a robust propensity to elicit the major manifestations of ICD in cultured neoplastic cells. This screen pointed to septacidin, an antibiotic produced by Streptomyces fibriatus, as a novel putative inducer of ICD. In low-throughput validation experiments, septacidin promoted CRT exposure, ATP secretion and HGMB1 release from both U2OS cells and murine fibrosarcoma MCA205 cells. Moreover, septacidin-killed MCA205 cells protected immunocompetent mice against a re-challenge with living cancer cells of the same type. Finally, the antineoplastic effects of septacidin on established murine tumors were entirely dependent on T lymphocytes. Altogether, these results underscore the suitability of the high-throughput screening system described here for the identification of novel ICD inducers.

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“…74,129,130 In this setting, 15 individuals with metastatic non-small cell lung carcinoma achieving disease stabilization upon standard-of-care chemotherapy received an IDO1derived peptide s.c. in combination with the Toll-like receptor 7 (TLR7) agonist imiquimod. 131,132 No severe side effects were recorded, 1 patient achieved a partial response one year after vaccination, and 6 patients experienced prolonged (>8.5 months) disease stabilization. Moreover, the overall survival of these individuals was significantly improved as compared to that of similar patients excluded from the study owing to HLA expression profile.…”

Section: Preclinical and Clinical Development Of Ido1 Inhibitors For mentioning

confidence: 98%

Trial watch: IDO inhibitors in cancer therapy

et al. 2014

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Indoleamine 2,3-dioxigenase 1 (IDO1) is the main enzyme that catalyzes the first, rate-limiting step of the so-called "kynurenine pathway", i.e., the metabolic cascade that converts the essential amino acid -tryptophan (Trp) into-kynurenine (Kyn). IDO1, which is expressed constitutively by some tissues and in an inducible manner by specific subsets of antigen-presenting cells, has been shown to play a role in the establishment and maintenance of peripheral tolerance. At least in part, this reflects the capacity of IDO1 to restrict the microenvironmental availability of Trp and to favor the accumulation of Kyn and some of its derivatives. Also, several neoplastic lesions express IDO1, providing them with a means to evade anticancer immunosurveillance. This consideration has driven the development of several IDO1 inhibitors, some of which (including 1-methyltryptophan) have nowadays entered clinical evaluation. In animal tumor models, the inhibition of IDO1 by chemical or genetic interventions is indeed associated with the (re)activation of therapeutically relevant anticancer immune responses. This said, several immunotherapeutic regimens exert robust clinical activity in spite of their ability to promote the expression of IDO1. Moreover, 1-methyltryptophan has recently been shown to exert IDO1-independent immunostimulatory effects. Here, we summarize the preclinical and clinical studies testing the antineoplastic activity of IDO1-targeting interventions.

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Trial Watch

Cited by 130 publications

References 264 publications

Pam2 lipopeptides systemically increase myeloid-derived suppressor cells through TLR2 signaling

Pam2 lipopeptides systemically increase myeloid-derived suppressor cells through TLR2 signaling

Screening of novel immunogenic cell death inducers within the NCI Mechanistic Diversity Set

Trial watch: IDO inhibitors in cancer therapy

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